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{{Other uses|LCK (disambiguation){{!}}LCK}}
{{Other uses|LCK (disambiguation){{!}}LCK}}
{{refimprove|date=April 2012}}
{{more citations needed|date=April 2012}}
{{Infobox_gene}}
{{Infobox_gene}}


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== T cell signaling ==
== T cell signaling ==


Lck is most commonly found in [[T cell]]s.  It associates with the [[cytoplasm]]ic tails of the [[CD4]] and [[CD8]] [[co-receptors]] on [[T helper cells]] and [[cytotoxic T cells]],<ref>{{cite journal | vauthors = Rudd CE, Trevillyan JM, Dasgupta JD, Wong LL, Schlossman SF | title = The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 14 | pages = 5190–4 | date = Jul 1988 | pmid = 2455897 | doi=10.1073/pnas.85.14.5190 | pmc=281714}}</ref><ref>{{cite journal | vauthors = Barber EK, Dasgupta JD, Schlossman SF, Trevillyan JM, Rudd CE | title = The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 86 | issue = 9 | pages = 3277–81 | date = May 1989 | pmid = 2470098 | doi=10.1073/pnas.86.9.3277 | pmc=287114}}</ref> respectively, to assist signaling from the [[T cell receptor]] (TCR) complex. When the [[T cell receptor]] is engaged by the specific [[antigen]] presented by [[Major histocompatibility complex|MHC]], Lck acts to [[phosphorylate]] the intracellular chains of the [[CD3 receptor|CD3]] and ζ-chains of the TCR complex, allowing another [[cytoplasm]]ic [[tyrosine]] [[kinase]] called [[ZAP-70]] to bind to them. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates another molecule in the signaling cascade called [[Linker of Activated T cells|LAT]] (short for Linker of Activated T cells), a [[transmembrane protein]] that serves as a docking site for a number of other proteins, the most important of which are [[SH2 domain|Shc]]-[[Grb2]]-SOS, [[PI3K]], and [[phospholipase C]] (PLC). Additionally, upon T cell activation, a fraction of kinase active Lck, translocates from outside of [[lipid raft]]s (LR) to inside lipid rafts where it interacts with and activates LR-resident [[FYN|Fyn]], which is involved in further downstream signaling activation.<ref>{{cite journal | vauthors = Filipp D, Zhang J, Leung BL, Shaw A, Levin SD, Veillette A, Julius M | title = Regulation of Fyn through translocation of activated Lck into lipid rafts | language = en | journal = The Journal of Experimental Medicine | volume = 197 | issue = 9 | pages = 1221–7 | date = May 2003 | pmid = 12732664 | pmc = 2193969 | doi = 10.1084/jem.20022112 }}</ref><ref>{{cite journal | vauthors = Filipp D, Moemeni B, Ferzoco A, Kathirkamathamby K, Zhang J, Ballek O, Davidson D, Veillette A, Julius M | title = Lck-dependent Fyn activation requires C terminus-dependent targeting of kinase-active Lck to lipid rafts | language = en | journal = The Journal of Biological Chemistry | volume = 283 | issue = 39 | pages = 26409–22 | date = Sep 2008 | pmid = 18660530 | pmc = 3258908 | doi = 10.1074/jbc.M710372200 }}</ref>
Lck is most commonly found in [[T cell]]s.  It associates with the [[cytoplasm]]ic tails of the [[CD4]] and [[CD8]] [[co-receptors]] on [[T helper cells]] and [[cytotoxic T cells]],<ref>{{cite journal | vauthors = Rudd CE, Trevillyan JM, Dasgupta JD, Wong LL, Schlossman SF | title = The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 14 | pages = 5190–4 | date = July 1988 | pmid = 2455897 | pmc = 281714 | doi = 10.1073/pnas.85.14.5190 }}</ref><ref>{{cite journal | vauthors = Barber EK, Dasgupta JD, Schlossman SF, Trevillyan JM, Rudd CE | title = The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 86 | issue = 9 | pages = 3277–81 | date = May 1989 | pmid = 2470098 | pmc = 287114 | doi = 10.1073/pnas.86.9.3277 }}</ref> respectively, to assist signaling from the [[T cell receptor]] (TCR) complex. When the [[T cell receptor]] is engaged by the specific [[antigen]] presented by [[Major histocompatibility complex|MHC]], Lck acts to [[phosphorylate]] the intracellular chains of the [[CD3 receptor|CD3]] and ζ-chains of the TCR complex, allowing another [[cytoplasm]]ic [[tyrosine]] [[kinase]] called [[ZAP-70]] to bind to them. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates another molecule in the signaling cascade called [[Linker of Activated T cells|LAT]] (short for Linker of Activated T cells), a [[transmembrane protein]] that serves as a docking site for a number of other proteins, the most important of which are [[SH2 domain|Shc]]-[[Grb2]]-SOS, [[PI3K]], and [[phospholipase C]] (PLC). Additionally, upon T cell activation, a fraction of kinase active Lck, translocates from outside of [[lipid raft]]s (LR) to inside lipid rafts where it interacts with and activates LR-resident [[FYN|Fyn]], which is involved in further downstream signaling activation.<ref>{{cite journal | vauthors = Filipp D, Zhang J, Leung BL, Shaw A, Levin SD, Veillette A, Julius M | title = Regulation of Fyn through translocation of activated Lck into lipid rafts | journal = The Journal of Experimental Medicine | volume = 197 | issue = 9 | pages = 1221–7 | date = May 2003 | pmid = 12732664 | pmc = 2193969 | doi = 10.1084/jem.20022112 }}</ref><ref>{{cite journal | vauthors = Filipp D, Moemeni B, Ferzoco A, Kathirkamathamby K, Zhang J, Ballek O, Davidson D, Veillette A, Julius M | title = Lck-dependent Fyn activation requires C terminus-dependent targeting of kinase-active Lck to lipid rafts | journal = The Journal of Biological Chemistry | volume = 283 | issue = 39 | pages = 26409–22 | date = September 2008 | pmid = 18660530 | pmc = 3258908 | doi = 10.1074/jbc.M710372200 }}</ref>


The tyrosine phosphorylation [[Biochemical cascade|cascade]] initiated by Lck and Fyn culminates in the intracellular mobilization of [[calcium]] (Ca<sup>2+</sup>) [[ion]]s and activation of important signaling cascades within the lymphocyte.  These include the [[Ras subfamily|Ras]]-[[Mitogen-activated protein kinase|MEK]]-[[Extracellular signal-regulated kinases|ERK]] pathway, which goes on to activate certain [[transcription factor]]s such as [[NFAT]], [[NF-κB]], and [[AP-1 (transcription factor)|AP-1]].  These transcription factors regulate the production of a [[wikt:plethora|plethora]] of gene products, most notable, [[cytokine]]s such as [[Interleukin-2]] that promote long-term proliferation and differentiation of the activated lymphocytes.
The tyrosine phosphorylation [[Biochemical cascade|cascade]] initiated by Lck and Fyn culminates in the intracellular mobilization of [[calcium]] (Ca<sup>2+</sup>) [[ion]]s and activation of important signaling cascades within the lymphocyte.  These include the [[Ras subfamily|Ras]]-[[Mitogen-activated protein kinase|MEK]]-[[Extracellular signal-regulated kinases|ERK]] pathway, which goes on to activate certain [[transcription factor]]s such as [[NFAT]], [[NF-κB]], and [[AP-1 (transcription factor)|AP-1]].  These transcription factors regulate the production of a [[wikt:plethora|plethora]] of gene products, most notable, [[cytokine]]s such as [[Interleukin-2]] that promote long-term proliferation and differentiation of the activated lymphocytes.
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== Inhibition ==
== Inhibition ==


In resting T cells, Lck is constitutively inhibited by Csk phosphorylation on tyrosine 505. Lck is also inhibited by [[SHP-1]] dephosphorylation on tyrosine 394. Lck can also be inhibited by [[Cbl ubiquitin ligase]], which is part of the [[ubiquitin]]-mediated pathway.<ref>{{cite journal | vauthors = Rao N, Miyake S, Reddi AL, Douillard P, Ghosh AK, Dodge IL, Zhou P, Fernandes ND, Band H | title = Negative regulation of Lck by Cbl ubiquitin ligase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 6 | pages = 3794–9 | date = Mar 2002 | pmid = 11904433 | doi = 10.1073/pnas.062055999 | pmc=122603}}</ref>
In resting T cells, Lck is constitutively inhibited by Csk phosphorylation on tyrosine 505. Lck is also inhibited by [[SHP-1]] dephosphorylation on tyrosine 394. Lck can also be inhibited by [[Cbl ubiquitin ligase]], which is part of the [[ubiquitin]]-mediated pathway.<ref>{{cite journal | vauthors = Rao N, Miyake S, Reddi AL, Douillard P, Ghosh AK, Dodge IL, Zhou P, Fernandes ND, Band H | title = Negative regulation of Lck by Cbl ubiquitin ligase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 6 | pages = 3794–9 | date = March 2002 | pmid = 11904433 | pmc = 122603 | doi = 10.1073/pnas.062055999 }}</ref>
 
Saractinib, a specific inhibitor of LCK impairs maintenance of human T-ALL cells in vitro as well as in vivo by targeting this tyrosine kinase in cells displaying high level of lipid rafts.<ref name = "Buffière_2018">{{cite journal | vauthors = Buffière A, Accogli T, Saint-Paul L, Lucchi G, Uzan B, Ballerini P, Bastie JN, Delva L, Pflumio F, Quéré R | title = Saracatinib impairs maintenance of human T-ALL by targeting the LCK tyrosine kinase in cells displaying high level of lipid rafts | journal = Leukemia | date = February 2018 | pmid = 29535432 | doi = 10.1038/s41375-018-0081-5 }}</ref>
 
[[Masitinib]] also inhibits Lck, which may have some impact on its therapeutic effects in canine [[mastocytoma]].<ref>{{cite journal | vauthors = Gil da Costa RM | title = C-kit as a prognostic and therapeutic marker in canine cutaneous mast cell tumours: From laboratory to clinic | journal = Veterinary Journal | volume = 205 | issue = 1 | pages = 5–10 | date = July 2015 | pmid = 26021891 | doi = 10.1016/j.tvjl.2015.05.002 }}</ref>


== Interactions ==
== Interactions ==
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Lck has been shown to [[Protein-protein interaction|interact]] with:
Lck has been shown to [[Protein-protein interaction|interact]] with:
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{{div col|colwidth=20em}}
* [[ADAM15]],<ref name = pmid11741929>{{cite journal | vauthors = Poghosyan Z, Robbins SM, Houslay MD, Webster A, Murphy G, Edwards DR | title = Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases | journal = The Journal of Biological Chemistry | volume = 277 | issue = 7 | pages = 4999–5007 | date = Feb 2002 | pmid = 11741929 | doi = 10.1074/jbc.M107430200 }}</ref>  
* [[ADAM15]],<ref name = pmid11741929>{{cite journal | vauthors = Poghosyan Z, Robbins SM, Houslay MD, Webster A, Murphy G, Edwards DR | title = Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases | journal = The Journal of Biological Chemistry | volume = 277 | issue = 7 | pages = 4999–5007 | date = February 2002 | pmid = 11741929 | doi = 10.1074/jbc.M107430200 }}</ref>  
* [[CD2]],<ref name = pmid8551220>{{cite journal | vauthors = Bell GM, Fargnoli J, Bolen JB, Kish L, Imboden JB | title = The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2 | journal = The Journal of Experimental Medicine | volume = 183 | issue = 1 | pages = 169–78 | date = Jan 1996 | pmid = 8551220 | pmc = 2192399 | doi = 10.1084/jem.183.1.169}}</ref>  
* [[CD2]],<ref name = pmid8551220>{{cite journal | vauthors = Bell GM, Fargnoli J, Bolen JB, Kish L, Imboden JB | title = The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2 | journal = The Journal of Experimental Medicine | volume = 183 | issue = 1 | pages = 169–78 | date = January 1996 | pmid = 8551220 | pmc = 2192399 | doi = 10.1084/jem.183.1.169 }}</ref>  
* [[CD44]],<ref name = pmid8576267>{{cite journal | vauthors = Taher TE, Smit L, Griffioen AW, Schilder-Tol EJ, Borst J, Pals ST | title = Signaling through CD44 is mediated by tyrosine kinases. Association with p56lck in T lymphocytes | journal = The Journal of Biological Chemistry | volume = 271 | issue = 5 | pages = 2863–7 | date = Feb 1996 | pmid = 8576267 | doi = 10.1074/jbc.271.5.2863}}</ref><ref name = pmid9573028>{{cite journal | vauthors = Ilangumaran S, Briol A, Hoessli DC | title = CD44 selectively associates with active Src family protein tyrosine kinases Lck and Fyn in glycosphingolipid-rich plasma membrane domains of human peripheral blood lymphocytes | journal = Blood | volume = 91 | issue = 10 | pages = 3901–8 | date = May 1998 | pmid = 9573028 | doi =  }}</ref>  
* [[CD44]],<ref name = pmid8576267>{{cite journal | vauthors = Taher TE, Smit L, Griffioen AW, Schilder-Tol EJ, Borst J, Pals ST | title = Signaling through CD44 is mediated by tyrosine kinases. Association with p56lck in T lymphocytes | journal = The Journal of Biological Chemistry | volume = 271 | issue = 5 | pages = 2863–7 | date = February 1996 | pmid = 8576267 | doi = 10.1074/jbc.271.5.2863 }}</ref><ref name = pmid9573028>{{cite journal | vauthors = Ilangumaran S, Briol A, Hoessli DC | title = CD44 selectively associates with active Src family protein tyrosine kinases Lck and Fyn in glycosphingolipid-rich plasma membrane domains of human peripheral blood lymphocytes | journal = Blood | volume = 91 | issue = 10 | pages = 3901–8 | date = May 1998 | pmid = 9573028 | doi =  }}</ref>  
* [[CD4]],<ref name = pmid12007789>{{cite journal | vauthors = Hawash IY, Hu XE, Adal A, Cassady JM, Geahlen RL, Harrison ML | title = The oxygen-substituted palmitic acid analogue, 13-oxypalmitic acid, inhibits Lck localization to lipid rafts and T cell signaling | journal = Biochimica et Biophysica Acta | volume = 1589 | issue = 2 | pages = 140–50 | date = Apr 2002 | pmid = 12007789 | doi = 10.1016/s0167-4889(02)00165-9}}</ref><ref name = pmid11854499>{{cite journal | vauthors = Foti M, Phelouzat MA, Holm A, Rasmusson BJ, Carpentier JL | title = p56Lck anchors CD4 to distinct microdomains on microvilli | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 4 | pages = 2008–13 | date = Feb 2002 | pmid = 11854499 | pmc = 122310 | doi = 10.1073/pnas.042689099 }}</ref>  
* [[CD4]],<ref name = pmid12007789>{{cite journal | vauthors = Hawash IY, Hu XE, Adal A, Cassady JM, Geahlen RL, Harrison ML | title = The oxygen-substituted palmitic acid analogue, 13-oxypalmitic acid, inhibits Lck localization to lipid rafts and T cell signaling | journal = Biochimica et Biophysica Acta | volume = 1589 | issue = 2 | pages = 140–50 | date = April 2002 | pmid = 12007789 | doi = 10.1016/s0167-4889(02)00165-9 }}</ref><ref name = pmid11854499>{{cite journal | vauthors = Foti M, Phelouzat MA, Holm A, Rasmusson BJ, Carpentier JL | title = p56Lck anchors CD4 to distinct microdomains on microvilli | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 4 | pages = 2008–13 | date = February 2002 | pmid = 11854499 | pmc = 122310 | doi = 10.1073/pnas.042689099 }}</ref>  
* [[COUP-TFII]],<ref name = pmid8910285>{{cite journal | vauthors = Marcus SL, Winrow CJ, Capone JP, Rachubinski RA | title = A p56(lck) ligand serves as a coactivator of an orphan nuclear hormone receptor | journal = The Journal of Biological Chemistry | volume = 271 | issue = 44 | pages = 27197–200 | date = Nov 1996 | pmid = 8910285 | doi = 10.1074/jbc.271.44.27197}}</ref>
* [[COUP-TFII]],<ref name = pmid8910285>{{cite journal | vauthors = Marcus SL, Winrow CJ, Capone JP, Rachubinski RA | title = A p56(lck) ligand serves as a coactivator of an orphan nuclear hormone receptor | journal = The Journal of Biological Chemistry | volume = 271 | issue = 44 | pages = 27197–200 | date = November 1996 | pmid = 8910285 | doi = 10.1074/jbc.271.44.27197 }}</ref>
* [[DLG1]],<ref name = pmid9341123>{{cite journal | vauthors = Hanada T, Lin L, Chandy KG, Oh SS, Chishti AH | title = Human homologue of the Drosophila discs large tumor suppressor binds to p56lck tyrosine kinase and Shaker type Kv1.3 potassium channel in T lymphocytes | journal = The Journal of Biological Chemistry | volume = 272 | issue = 43 | pages = 26899–904 | date = Oct 1997 | pmid = 9341123 | doi = 10.1074/jbc.272.43.26899}}</ref>  
* [[DLG1]],<ref name = pmid9341123>{{cite journal | vauthors = Hanada T, Lin L, Chandy KG, Oh SS, Chishti AH | title = Human homologue of the Drosophila discs large tumor suppressor binds to p56lck tyrosine kinase and Shaker type Kv1.3 potassium channel in T lymphocytes | journal = The Journal of Biological Chemistry | volume = 272 | issue = 43 | pages = 26899–904 | date = October 1997 | pmid = 9341123 | doi = 10.1074/jbc.272.43.26899 }}</ref>  
* [[NOTCH1]],<ref name = pmid14583609/>
* [[NOTCH1]],<ref name = pmid14583609/>
* [[P110α|PIK3CA]],<ref name = pmid14583609>{{cite journal | vauthors = Sade H, Krishna S, Sarin A | title = The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated signaling in T cells | journal = The Journal of Biological Chemistry | volume = 279 | issue = 4 | pages = 2937–44 | date = Jan 2004 | pmid = 14583609 | doi = 10.1074/jbc.M309924200 }}</ref><ref name = pmid8246987>{{cite journal | vauthors = Prasad KV, Kapeller R, Janssen O, Repke H, Duke-Cohan JS, Cantley LC, Rudd CE | title = Phosphatidylinositol (PI) 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase | journal = Molecular and Cellular Biology | volume = 13 | issue = 12 | pages = 7708–17 | date = Dec 1993 | pmid = 8246987 | pmc = 364842 | doi = 10.1128/mcb.13.12.7708}}</ref>  
* [[P110α|PIK3CA]],<ref name = pmid14583609>{{cite journal | vauthors = Sade H, Krishna S, Sarin A | title = The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated signaling in T cells | journal = The Journal of Biological Chemistry | volume = 279 | issue = 4 | pages = 2937–44 | date = January 2004 | pmid = 14583609 | doi = 10.1074/jbc.M309924200 }}</ref><ref name = pmid8246987>{{cite journal | vauthors = Prasad KV, Kapeller R, Janssen O, Repke H, Duke-Cohan JS, Cantley LC, Rudd CE | title = Phosphatidylinositol (PI) 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase | journal = Molecular and Cellular Biology | volume = 13 | issue = 12 | pages = 7708–17 | date = December 1993 | pmid = 8246987 | pmc = 364842 | doi = 10.1128/mcb.13.12.7708 }}</ref>  
* [[PTPN6]],<ref name = pmid10617656>{{cite journal | vauthors = Yu CL, Jin YJ, Burakoff SJ | title = Cytosolic tyrosine dephosphorylation of STAT5. Potential role of SHP-2 in STAT5 regulation | journal = The Journal of Biological Chemistry | volume = 275 | issue = 1 | pages = 599–604 | date = Jan 2000 | pmid = 10617656 | doi = 10.1074/jbc.275.1.599}}</ref><ref name = pmid11294838>{{cite journal | vauthors = Chiang GG, Sefton BM | title = Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase | journal = The Journal of Biological Chemistry | volume = 276 | issue = 25 | pages = 23173–8 | date = Jun 2001 | pmid = 11294838 | doi = 10.1074/jbc.M101219200 }}</ref><ref name = pmid8114715>{{cite journal | vauthors = Lorenz U, Ravichandran KS, Pei D, Walsh CT, Burakoff SJ, Neel BG | title = Lck-dependent tyrosyl phosphorylation of the phosphotyrosine phosphatase SH-PTP1 in murine T cells | journal = Molecular and Cellular Biology | volume = 14 | issue = 3 | pages = 1824–34 | date = Mar 1994 | pmid = 8114715 | pmc = 358540 | doi = 10.1128/mcb.14.3.1824}}</ref>  
* [[PTPN6]],<ref name = pmid10617656>{{cite journal | vauthors = Yu CL, Jin YJ, Burakoff SJ | title = Cytosolic tyrosine dephosphorylation of STAT5. Potential role of SHP-2 in STAT5 regulation | journal = The Journal of Biological Chemistry | volume = 275 | issue = 1 | pages = 599–604 | date = January 2000 | pmid = 10617656 | doi = 10.1074/jbc.275.1.599 }}</ref><ref name = pmid11294838>{{cite journal | vauthors = Chiang GG, Sefton BM | title = Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase | journal = The Journal of Biological Chemistry | volume = 276 | issue = 25 | pages = 23173–8 | date = June 2001 | pmid = 11294838 | doi = 10.1074/jbc.M101219200 }}</ref><ref name = pmid8114715>{{cite journal | vauthors = Lorenz U, Ravichandran KS, Pei D, Walsh CT, Burakoff SJ, Neel BG | title = Lck-dependent tyrosyl phosphorylation of the phosphotyrosine phosphatase SH-PTP1 in murine T cells | journal = Molecular and Cellular Biology | volume = 14 | issue = 3 | pages = 1824–34 | date = March 1994 | pmid = 8114715 | pmc = 358540 | doi = 10.1128/mcb.14.3.1824 }}</ref>  
* [[PTPRC]],<ref name = pmid8473339>{{cite journal | vauthors = Koretzky GA, Kohmetscher M, Ross S | title = CD45-associated kinase activity requires lck but not T cell receptor expression in the Jurkat T cell line | journal = The Journal of Biological Chemistry | volume = 268 | issue = 12 | pages = 8958–64 | date = Apr 1993 | pmid = 8473339 | doi =  }}</ref><ref name = pmid8576115>{{cite journal | vauthors = Ng DH, Watts JD, Aebersold R, Johnson P | title = Demonstration of a direct interaction between p56lck and the cytoplasmic domain of CD45 in vitro | journal = The Journal of Biological Chemistry | volume = 271 | issue = 3 | pages = 1295–300 | date = Jan 1996 | pmid = 8576115 | doi = 10.1074/jbc.271.3.1295}}</ref>  
* [[PTPRC]],<ref name = pmid8473339>{{cite journal | vauthors = Koretzky GA, Kohmetscher M, Ross S | title = CD45-associated kinase activity requires lck but not T cell receptor expression in the Jurkat T cell line | journal = The Journal of Biological Chemistry | volume = 268 | issue = 12 | pages = 8958–64 | date = April 1993 | pmid = 8473339 | doi =  }}</ref><ref name = pmid8576115>{{cite journal | vauthors = Ng DH, Watts JD, Aebersold R, Johnson P | title = Demonstration of a direct interaction between p56lck and the cytoplasmic domain of CD45 in vitro | journal = The Journal of Biological Chemistry | volume = 271 | issue = 3 | pages = 1295–300 | date = January 1996 | pmid = 8576115 | doi = 10.1074/jbc.271.3.1295 }}</ref>  
* [[Protein unc-119 homolog|UNC119]],<ref name = pmid14757743>{{cite journal | vauthors = Gorska MM, Stafford SJ, Cen O, Sur S, Alam R | title = Unc119, a novel activator of Lck/Fyn, is essential for T cell activation | journal = The Journal of Experimental Medicine | volume = 199 | issue = 3 | pages = 369–79 | date = Feb 2004 | pmid = 14757743 | pmc = 2211793 | doi = 10.1084/jem.20030589 }}</ref>  
* [[Protein unc-119 homolog|UNC119]],<ref name = pmid14757743>{{cite journal | vauthors = Gorska MM, Stafford SJ, Cen O, Sur S, Alam R | title = Unc119, a novel activator of Lck/Fyn, is essential for T cell activation | journal = The Journal of Experimental Medicine | volume = 199 | issue = 3 | pages = 369–79 | date = February 2004 | pmid = 14757743 | pmc = 2211793 | doi = 10.1084/jem.20030589 }}</ref>  
* [[Syk|SYK]],<ref name = pmid7539035/>  
* [[Syk|SYK]],<ref name = pmid7539035/>  
* [[UBE3A]],<ref name = pmid10449731>{{cite journal | vauthors = Oda H, Kumar S, Howley PM | title = Regulation of the Src family tyrosine kinase Blk through E6AP-mediated ubiquitination | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 17 | pages = 9557–62 | date = Aug 1999 | pmid = 10449731 | pmc = 22247 | doi = 10.1073/pnas.96.17.9557}}</ref>  and
* [[UBE3A]],<ref name = pmid10449731>{{cite journal | vauthors = Oda H, Kumar S, Howley PM | title = Regulation of the Src family tyrosine kinase Blk through E6AP-mediated ubiquitination | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 17 | pages = 9557–62 | date = August 1999 | pmid = 10449731 | pmc = 22247 | doi = 10.1073/pnas.96.17.9557 }}</ref>  and
* [[ZAP70]].<ref name = pmid7539035>{{cite journal | vauthors = Thome M, Duplay P, Guttinger M, Acuto O | title = Syk and ZAP-70 mediate recruitment of p56lck/CD4 to the activated T cell receptor/CD3/zeta complex | journal = The Journal of Experimental Medicine | volume = 181 | issue = 6 | pages = 1997–2006 | date = Jun 1995 | pmid = 7539035 | pmc = 2192070 | doi = 10.1084/jem.181.6.1997}}</ref><ref name = pmid10318843>{{cite journal | vauthors = Pelosi M, Di Bartolo V, Mounier V, Mège D, Pascussi JM, Dufour E, Blondel A, Acuto O | title = Tyrosine 319 in the interdomain B of ZAP-70 is a binding site for the Src homology 2 domain of Lck | journal = The Journal of Biological Chemistry | volume = 274 | issue = 20 | pages = 14229–37 | date = May 1999 | pmid = 10318843 | doi = 10.1074/jbc.274.20.14229}}</ref>  
* [[ZAP70]].<ref name = pmid7539035>{{cite journal | vauthors = Thome M, Duplay P, Guttinger M, Acuto O | title = Syk and ZAP-70 mediate recruitment of p56lck/CD4 to the activated T cell receptor/CD3/zeta complex | journal = The Journal of Experimental Medicine | volume = 181 | issue = 6 | pages = 1997–2006 | date = June 1995 | pmid = 7539035 | pmc = 2192070 | doi = 10.1084/jem.181.6.1997 }}</ref><ref name = pmid10318843>{{cite journal | vauthors = Pelosi M, Di Bartolo V, Mounier V, Mège D, Pascussi JM, Dufour E, Blondel A, Acuto O | title = Tyrosine 319 in the interdomain B of ZAP-70 is a binding site for the Src homology 2 domain of Lck | journal = The Journal of Biological Chemistry | volume = 274 | issue = 20 | pages = 14229–37 | date = May 1999 | pmid = 10318843 | doi = 10.1074/jbc.274.20.14229 }}</ref>  
{{Div col end}}
{{Div col end}}


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== Further reading ==
== Further reading ==
{{refbegin|33em}}
{{refbegin|33em}}
* {{cite journal | vauthors = Sasaoka T, Kobayashi M | title = The functional significance of Shc in insulin signaling as a substrate of the insulin receptor | journal = Endocrine Journal | volume = 47 | issue = 4 | pages = 373–81 | date = Aug 2000 | pmid = 11075717 | doi = 10.1507/endocrj.47.373 }}
* {{cite journal | vauthors = Sasaoka T, Kobayashi M | title = The functional significance of Shc in insulin signaling as a substrate of the insulin receptor | journal = Endocrine Journal | volume = 47 | issue = 4 | pages = 373–81 | date = August 2000 | pmid = 11075717 | doi = 10.1507/endocrj.47.373 }}
* {{cite journal | vauthors = Goldmann WH | title = p56(lck) Controls phosphorylation of filamin (ABP-280) and regulates focal adhesion kinase (pp125(FAK)) | journal = Cell Biology International | volume = 26 | issue = 6 | pages = 567–71 | year = 2003 | pmid = 12171035 | doi = 10.1006/cbir.2002.0900 }}
* {{cite journal | vauthors = Goldmann WH | title = p56(lck) Controls phosphorylation of filamin (ABP-280) and regulates focal adhesion kinase (pp125(FAK)) | journal = Cell Biology International | volume = 26 | issue = 6 | pages = 567–71 | year = 2003 | pmid = 12171035 | doi = 10.1006/cbir.2002.0900 }}
* {{cite journal | vauthors = Mustelin T, Taskén K | title = Positive and negative regulation of T-cell activation through kinases and phosphatases | journal = The Biochemical Journal | volume = 371 | issue = Pt 1 | pages = 15–27 | date = Apr 2003 | pmid = 12485116 | pmc = 1223257 | doi = 10.1042/BJ20021637 }}
* {{cite journal | vauthors = Mustelin T, Taskén K | title = Positive and negative regulation of T-cell activation through kinases and phosphatases | journal = The Biochemical Journal | volume = 371 | issue = Pt 1 | pages = 15–27 | date = April 2003 | pmid = 12485116 | pmc = 1223257 | doi = 10.1042/BJ20021637 }}
* {{cite journal | vauthors = Zamoyska R, Basson A, Filby A, Legname G, Lovatt M, Seddon B | title = The influence of the src-family kinases, Lck and Fyn, on T cell differentiation, survival and activation | journal = Immunological Reviews | volume = 191 | issue =  | pages = 107–18 | date = Feb 2003 | pmid = 12614355 | doi = 10.1034/j.1600-065X.2003.00015.x }}
* {{cite journal | vauthors = Zamoyska R, Basson A, Filby A, Legname G, Lovatt M, Seddon B | title = The influence of the src-family kinases, Lck and Fyn, on T cell differentiation, survival and activation | journal = Immunological Reviews | volume = 191 | issue =  | pages = 107–18 | date = February 2003 | pmid = 12614355 | doi = 10.1034/j.1600-065X.2003.00015.x }}
* {{cite journal | vauthors = Summy JM, Gallick GE | title = Src family kinases in tumor progression and metastasis | journal = Cancer Metastasis Reviews | volume = 22 | issue = 4 | pages = 337–58 | date = Dec 2003 | pmid = 12884910 | doi = 10.1023/A:1023772912750 }}
* {{cite journal | vauthors = Summy JM, Gallick GE | title = Src family kinases in tumor progression and metastasis | journal = Cancer Metastasis Reviews | volume = 22 | issue = 4 | pages = 337–58 | date = December 2003 | pmid = 12884910 | doi = 10.1023/A:1023772912750 }}
* {{cite journal | vauthors = Leavitt SA, SchOn A, Klein JC, Manjappara U, Chaiken IM, Freire E | title = Interactions of HIV-1 proteins gp120 and Nef with cellular partners define a novel allosteric paradigm | journal = Current Protein & Peptide Science | volume = 5 | issue = 1 | pages = 1–8 | date = Feb 2004 | pmid = 14965316 | doi = 10.2174/1389203043486955 }}
* {{cite journal | vauthors = Leavitt SA, SchOn A, Klein JC, Manjappara U, Chaiken IM, Freire E | title = Interactions of HIV-1 proteins gp120 and Nef with cellular partners define a novel allosteric paradigm | journal = Current Protein & Peptide Science | volume = 5 | issue = 1 | pages = 1–8 | date = February 2004 | pmid = 14965316 | doi = 10.2174/1389203043486955 }}
* {{cite journal | vauthors = Tolstrup M, Ostergaard L, Laursen AL, Pedersen SF, Duch M | title = HIV/SIV escape from immune surveillance: focus on Nef | journal = Current HIV Research | volume = 2 | issue = 2 | pages = 141–51 | date = Apr 2004 | pmid = 15078178 | doi = 10.2174/1570162043484924 }}
* {{cite journal | vauthors = Tolstrup M, Ostergaard L, Laursen AL, Pedersen SF, Duch M | title = HIV/SIV escape from immune surveillance: focus on Nef | journal = Current HIV Research | volume = 2 | issue = 2 | pages = 141–51 | date = April 2004 | pmid = 15078178 | doi = 10.2174/1570162043484924 }}
* {{cite journal | vauthors = Palacios EH, Weiss A | title = Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation | journal = Oncogene | volume = 23 | issue = 48 | pages = 7990–8000 | date = Oct 2004 | pmid = 15489916 | doi = 10.1038/sj.onc.1208074 }}
* {{cite journal | vauthors = Palacios EH, Weiss A | title = Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation | journal = Oncogene | volume = 23 | issue = 48 | pages = 7990–8000 | date = October 2004 | pmid = 15489916 | doi = 10.1038/sj.onc.1208074 }}
* {{cite journal | vauthors = Joseph AM, Kumar M, Mitra D | title = Nef: "necessary and enforcing factor" in HIV infection | journal = Current HIV Research | volume = 3 | issue = 1 | pages = 87–94 | date = Jan 2005 | pmid = 15638726 | doi = 10.2174/1570162052773013 }}
* {{cite journal | vauthors = Joseph AM, Kumar M, Mitra D | title = Nef: "necessary and enforcing factor" in HIV infection | journal = Current HIV Research | volume = 3 | issue = 1 | pages = 87–94 | date = January 2005 | pmid = 15638726 | doi = 10.2174/1570162052773013 }}
* {{cite journal | vauthors = Levinson AD, Oppermann H, Levintow L, Varmus HE, Bishop JM | title = Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein | journal = Cell | volume = 15 | issue = 2 | pages = 561–72 | date = Oct 1978 | pmid = 214242 | doi = 10.1016/0092-8674(78)90024-7 }}
* {{cite journal | vauthors = Levinson AD, Oppermann H, Levintow L, Varmus HE, Bishop JM | title = Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein | journal = Cell | volume = 15 | issue = 2 | pages = 561–72 | date = October 1978 | pmid = 214242 | doi = 10.1016/0092-8674(78)90024-7 }}
* {{cite journal | vauthors = Thomas PM, Samelson LE | title = The glycophosphatidylinositol-anchored Thy-1 molecule interacts with the p60fyn protein tyrosine kinase in T cells | journal = The Journal of Biological Chemistry | volume = 267 | issue = 17 | pages = 12317–22 | date = Jun 1992 | pmid = 1351058 | doi =  }}
* {{cite journal | vauthors = Thomas PM, Samelson LE | title = The glycophosphatidylinositol-anchored Thy-1 molecule interacts with the p60fyn protein tyrosine kinase in T cells | journal = The Journal of Biological Chemistry | volume = 267 | issue = 17 | pages = 12317–22 | date = June 1992 | pmid = 1351058 | doi =  }}
* {{cite journal | vauthors = Shenoy-Scaria AM, Kwong J, Fujita T, Olszowy MW, Shaw AS, Lublin DM | title = Signal transduction through decay-accelerating factor. Interaction of glycosyl-phosphatidylinositol anchor and protein tyrosine kinases p56lck and p59fyn 1 | journal = Journal of Immunology | volume = 149 | issue = 11 | pages = 3535–41 | date = Dec 1992 | pmid = 1385527 | doi =  }}
* {{cite journal | vauthors = Shenoy-Scaria AM, Kwong J, Fujita T, Olszowy MW, Shaw AS, Lublin DM | title = Signal transduction through decay-accelerating factor. Interaction of glycosyl-phosphatidylinositol anchor and protein tyrosine kinases p56lck and p59fyn 1 | journal = Journal of Immunology | volume = 149 | issue = 11 | pages = 3535–41 | date = December 1992 | pmid = 1385527 | doi =  }}
* {{cite journal | vauthors = Brown R, Meldrum C, Cousins S | title = Are sense-antisense peptide interactions between HIV-1 (gp120), CD4, and the proto oncogene product p56lck important? | journal = Medical Hypotheses | volume = 38 | issue = 4 | pages = 322–4 | date = Aug 1992 | pmid = 1491632 | doi = 10.1016/0306-9877(92)90025-8 }}
* {{cite journal | vauthors = Brown R, Meldrum C, Cousins S | title = Are sense-antisense peptide interactions between HIV-1 (gp120), CD4, and the proto oncogene product p56lck important? | journal = Medical Hypotheses | volume = 38 | issue = 4 | pages = 322–4 | date = August 1992 | pmid = 1491632 | doi = 10.1016/0306-9877(92)90025-8 }}
* {{cite journal | vauthors = Weber JR, Bell GM, Han MY, Pawson T, Imboden JB | title = Association of the tyrosine kinase LCK with phospholipase C-gamma 1 after stimulation of the T cell antigen receptor | journal = The Journal of Experimental Medicine | volume = 176 | issue = 2 | pages = 373–9 | date = Aug 1992 | pmid = 1500851 | pmc = 2119313 | doi = 10.1084/jem.176.2.373 }}
* {{cite journal | vauthors = Weber JR, Bell GM, Han MY, Pawson T, Imboden JB | title = Association of the tyrosine kinase LCK with phospholipase C-gamma 1 after stimulation of the T cell antigen receptor | journal = The Journal of Experimental Medicine | volume = 176 | issue = 2 | pages = 373–9 | date = August 1992 | pmid = 1500851 | pmc = 2119313 | doi = 10.1084/jem.176.2.373 }}
* {{cite journal | vauthors = Cefai D, Ferrer M, Serpente N, Idziorek T, Dautry-Varsat A, Debre P, Bismuth G | title = Internalization of HIV glycoprotein gp120 is associated with down-modulation of membrane CD4 and p56lck together with impairment of T cell activation | journal = Journal of Immunology | volume = 149 | issue = 1 | pages = 285–94 | date = Jul 1992 | pmid = 1535086 | doi =  }}
* {{cite journal | vauthors = Cefai D, Ferrer M, Serpente N, Idziorek T, Dautry-Varsat A, Debre P, Bismuth G | title = Internalization of HIV glycoprotein gp120 is associated with down-modulation of membrane CD4 and p56lck together with impairment of T cell activation | journal = Journal of Immunology | volume = 149 | issue = 1 | pages = 285–94 | date = July 1992 | pmid = 1535086 | doi =  }}
* {{cite journal | vauthors = Soula M, Fagard R, Fischer S | title = Interaction of human immunodeficiency virus glycoprotein 160 with CD4 in Jurkat cells increases p56lck autophosphorylation and kinase activity | journal = International Immunology | volume = 4 | issue = 2 | pages = 295–9 | date = Feb 1992 | pmid = 1535787 | doi = 10.1093/intimm/4.2.295 }}
* {{cite journal | vauthors = Soula M, Fagard R, Fischer S | title = Interaction of human immunodeficiency virus glycoprotein 160 with CD4 in Jurkat cells increases p56lck autophosphorylation and kinase activity | journal = [[International Immunology]] | volume = 4 | issue = 2 | pages = 295–9 | date = February 1992 | pmid = 1535787 | doi = 10.1093/intimm/4.2.295 }}
* {{cite journal | vauthors = Crise B, Rose JK | title = Human immunodeficiency virus type 1 glycoprotein precursor retains a CD4-p56lck complex in the endoplasmic reticulum | journal = Journal of Virology | volume = 66 | issue = 4 | pages = 2296–301 | date = Apr 1992 | pmid = 1548763 | pmc = 289024 | doi =  }}
* {{cite journal | vauthors = Crise B, Rose JK | title = Human immunodeficiency virus type 1 glycoprotein precursor retains a CD4-p56lck complex in the endoplasmic reticulum | journal = Journal of Virology | volume = 66 | issue = 4 | pages = 2296–301 | date = April 1992 | pmid = 1548763 | pmc = 289024 | doi =  }}
* {{cite journal | vauthors = Molina TJ, Kishihara K, Siderovski DP, van Ewijk W, Narendran A, Timms E, Wakeham A, Paige CJ, Hartmann KU, Veillette A | title = Profound block in thymocyte development in mice lacking p56lck | journal = Nature | volume = 357 | issue = 6374 | pages = 161–4 | date = May 1992 | pmid = 1579166 | doi = 10.1038/357161a0 }}
* {{cite journal | vauthors = Molina TJ, Kishihara K, Siderovski DP, van Ewijk W, Narendran A, Timms E, Wakeham A, Paige CJ, Hartmann KU, Veillette A | title = Profound block in thymocyte development in mice lacking p56lck | journal = Nature | volume = 357 | issue = 6374 | pages = 161–4 | date = May 1992 | pmid = 1579166 | doi = 10.1038/357161a0 }}
* {{cite journal | vauthors = Yoshida H, Koga Y, Moroi Y, Kimura G, Nomoto K | title = The effect of p56lck, a lymphocyte specific protein tyrosine kinase, on the syncytium formation induced by human immunodeficiency virus envelope glycoprotein | journal = International Immunology | volume = 4 | issue = 2 | pages = 233–42 | date = Feb 1992 | pmid = 1622897 | doi = 10.1093/intimm/4.2.233 }}
* {{cite journal | vauthors = Yoshida H, Koga Y, Moroi Y, Kimura G, Nomoto K | title = The effect of p56lck, a lymphocyte specific protein tyrosine kinase, on the syncytium formation induced by human immunodeficiency virus envelope glycoprotein | journal = International Immunology | volume = 4 | issue = 2 | pages = 233–42 | date = February 1992 | pmid = 1622897 | doi = 10.1093/intimm/4.2.233 }}
* {{cite journal | vauthors = Torigoe T, O'Connor R, Santoli D, Reed JC | title = Interleukin-3 regulates the activity of the LYN protein-tyrosine kinase in myeloid-committed leukemic cell lines | journal = Blood | volume = 80 | issue = 3 | pages = 617–24 | date = Aug 1992 | pmid = 1638019 | doi =  }}
* {{cite journal | vauthors = Torigoe T, O'Connor R, Santoli D, Reed JC | title = Interleukin-3 regulates the activity of the LYN protein-tyrosine kinase in myeloid-committed leukemic cell lines | journal = Blood | volume = 80 | issue = 3 | pages = 617–24 | date = August 1992 | pmid = 1638019 | doi =  }}
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Latest revision as of 05:15, 15 June 2018

For other uses, see LCK.
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Lck (or lymphocyte-specific protein tyrosine kinase) is a 56 kDa protein that is found inside specialized cells of the immune system called lymphocytes. Lck is a tyrosine kinase, which phosphorylates tyrosine residues of certain proteins involved in the intracellular signaling pathways of these lymphocytes. It is a member of the Src family of tyrosine kinases.

T cell signaling

Lck is most commonly found in T cells. It associates with the cytoplasmic tails of the CD4 and CD8 co-receptors on T helper cells and cytotoxic T cells,[1][2] respectively, to assist signaling from the T cell receptor (TCR) complex. When the T cell receptor is engaged by the specific antigen presented by MHC, Lck acts to phosphorylate the intracellular chains of the CD3 and ζ-chains of the TCR complex, allowing another cytoplasmic tyrosine kinase called ZAP-70 to bind to them. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates another molecule in the signaling cascade called LAT (short for Linker of Activated T cells), a transmembrane protein that serves as a docking site for a number of other proteins, the most important of which are Shc-Grb2-SOS, PI3K, and phospholipase C (PLC). Additionally, upon T cell activation, a fraction of kinase active Lck, translocates from outside of lipid rafts (LR) to inside lipid rafts where it interacts with and activates LR-resident Fyn, which is involved in further downstream signaling activation.[3][4]

The tyrosine phosphorylation cascade initiated by Lck and Fyn culminates in the intracellular mobilization of calcium (Ca2+) ions and activation of important signaling cascades within the lymphocyte. These include the Ras-MEK-ERK pathway, which goes on to activate certain transcription factors such as NFAT, NF-κB, and AP-1. These transcription factors regulate the production of a plethora of gene products, most notable, cytokines such as Interleukin-2 that promote long-term proliferation and differentiation of the activated lymphocytes.

The function of Lck has been studied using several biochemical methods, including gene knockout (knock-out mice), Jurkat cells deficient in Lck (JCaM1.6), and siRNA-mediated RNA interference.

Structure

Lck is a 56-kilodalton protein. The N-terminal tail of Lck is myristoylated and palmitoylated, which tethers the protein to the plasma membrane of the cell. The protein furthermore contains a SH3 domain, a SH2 domain and in the C-terminal part the tyrosine kinase domain. The two main phosphorylation sites on Lck are tyrosines 394 and 505. The former is an autophosphorylation site and is linked to activation of the protein. The latter is phosphorylated by Csk, which inhibits Lck because the protein folds up and binds its own SH2 domain. Lck thus serves as an instructive example that protein phosphorylation may result in both activation and inhibition.

Substrates

Lck tyrosine phosphorylates a number of proteins, the most important of which are the CD3 receptor, CEACAM1, ZAP-70, SLP-76, the IL-2 receptor, Protein kinase C, ITK, PLC, SHC, RasGAP, Cbl, Vav1, and PI3K.

Inhibition

In resting T cells, Lck is constitutively inhibited by Csk phosphorylation on tyrosine 505. Lck is also inhibited by SHP-1 dephosphorylation on tyrosine 394. Lck can also be inhibited by Cbl ubiquitin ligase, which is part of the ubiquitin-mediated pathway.[5]

Saractinib, a specific inhibitor of LCK impairs maintenance of human T-ALL cells in vitro as well as in vivo by targeting this tyrosine kinase in cells displaying high level of lipid rafts.[6]

Masitinib also inhibits Lck, which may have some impact on its therapeutic effects in canine mastocytoma.[7]

Interactions

Lck has been shown to interact with:

See also

References

  1. ↑ Rudd CE, Trevillyan JM, Dasgupta JD, Wong LL, Schlossman SF (July 1988). "The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes". Proceedings of the National Academy of Sciences of the United States of America. 85 (14): 5190–4. doi:10.1073/pnas.85.14.5190. PMC 281714. PMID 2455897.
  2. ↑ Barber EK, Dasgupta JD, Schlossman SF, Trevillyan JM, Rudd CE (May 1989). "The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex". Proceedings of the National Academy of Sciences of the United States of America. 86 (9): 3277–81. doi:10.1073/pnas.86.9.3277. PMC 287114. PMID 2470098.
  3. ↑ Filipp D, Zhang J, Leung BL, Shaw A, Levin SD, Veillette A, Julius M (May 2003). "Regulation of Fyn through translocation of activated Lck into lipid rafts". The Journal of Experimental Medicine. 197 (9): 1221–7. doi:10.1084/jem.20022112. PMC 2193969. PMID 12732664.
  4. ↑ Filipp D, Moemeni B, Ferzoco A, Kathirkamathamby K, Zhang J, Ballek O, Davidson D, Veillette A, Julius M (September 2008). "Lck-dependent Fyn activation requires C terminus-dependent targeting of kinase-active Lck to lipid rafts". The Journal of Biological Chemistry. 283 (39): 26409–22. doi:10.1074/jbc.M710372200. PMC 3258908. PMID 18660530.
  5. ↑ Rao N, Miyake S, Reddi AL, Douillard P, Ghosh AK, Dodge IL, Zhou P, Fernandes ND, Band H (March 2002). "Negative regulation of Lck by Cbl ubiquitin ligase". Proceedings of the National Academy of Sciences of the United States of America. 99 (6): 3794–9. doi:10.1073/pnas.062055999. PMC 122603. PMID 11904433.
  6. ↑ Buffière A, Accogli T, Saint-Paul L, Lucchi G, Uzan B, Ballerini P, Bastie JN, Delva L, Pflumio F, Quéré R (February 2018). "Saracatinib impairs maintenance of human T-ALL by targeting the LCK tyrosine kinase in cells displaying high level of lipid rafts". Leukemia. doi:10.1038/s41375-018-0081-5. PMID 29535432.
  7. ↑ Gil da Costa RM (July 2015). "C-kit as a prognostic and therapeutic marker in canine cutaneous mast cell tumours: From laboratory to clinic". Veterinary Journal. 205 (1): 5–10. doi:10.1016/j.tvjl.2015.05.002. PMID 26021891.
  8. ↑ Poghosyan Z, Robbins SM, Houslay MD, Webster A, Murphy G, Edwards DR (February 2002). "Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases". The Journal of Biological Chemistry. 277 (7): 4999–5007. doi:10.1074/jbc.M107430200. PMID 11741929.
  9. ↑ Bell GM, Fargnoli J, Bolen JB, Kish L, Imboden JB (January 1996). "The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2". The Journal of Experimental Medicine. 183 (1): 169–78. doi:10.1084/jem.183.1.169. PMC 2192399. PMID 8551220.
  10. ↑ Taher TE, Smit L, Griffioen AW, Schilder-Tol EJ, Borst J, Pals ST (February 1996). "Signaling through CD44 is mediated by tyrosine kinases. Association with p56lck in T lymphocytes". The Journal of Biological Chemistry. 271 (5): 2863–7. doi:10.1074/jbc.271.5.2863. PMID 8576267.
  11. ↑ Ilangumaran S, Briol A, Hoessli DC (May 1998). "CD44 selectively associates with active Src family protein tyrosine kinases Lck and Fyn in glycosphingolipid-rich plasma membrane domains of human peripheral blood lymphocytes". Blood. 91 (10): 3901–8. PMID 9573028.
  12. ↑ Hawash IY, Hu XE, Adal A, Cassady JM, Geahlen RL, Harrison ML (April 2002). "The oxygen-substituted palmitic acid analogue, 13-oxypalmitic acid, inhibits Lck localization to lipid rafts and T cell signaling". Biochimica et Biophysica Acta. 1589 (2): 140–50. doi:10.1016/s0167-4889(02)00165-9. PMID 12007789.
  13. ↑ Foti M, Phelouzat MA, Holm A, Rasmusson BJ, Carpentier JL (February 2002). "p56Lck anchors CD4 to distinct microdomains on microvilli". Proceedings of the National Academy of Sciences of the United States of America. 99 (4): 2008–13. doi:10.1073/pnas.042689099. PMC 122310. PMID 11854499.
  14. ↑ Marcus SL, Winrow CJ, Capone JP, Rachubinski RA (November 1996). "A p56(lck) ligand serves as a coactivator of an orphan nuclear hormone receptor". The Journal of Biological Chemistry. 271 (44): 27197–200. doi:10.1074/jbc.271.44.27197. PMID 8910285.
  15. ↑ Hanada T, Lin L, Chandy KG, Oh SS, Chishti AH (October 1997). "Human homologue of the Drosophila discs large tumor suppressor binds to p56lck tyrosine kinase and Shaker type Kv1.3 potassium channel in T lymphocytes". The Journal of Biological Chemistry. 272 (43): 26899–904. doi:10.1074/jbc.272.43.26899. PMID 9341123.
  16. ↑ 16.0 16.1 Sade H, Krishna S, Sarin A (January 2004). "The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated signaling in T cells". The Journal of Biological Chemistry. 279 (4): 2937–44. doi:10.1074/jbc.M309924200. PMID 14583609.
  17. ↑ Prasad KV, Kapeller R, Janssen O, Repke H, Duke-Cohan JS, Cantley LC, Rudd CE (December 1993). "Phosphatidylinositol (PI) 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase". Molecular and Cellular Biology. 13 (12): 7708–17. doi:10.1128/mcb.13.12.7708. PMC 364842. PMID 8246987.
  18. ↑ Yu CL, Jin YJ, Burakoff SJ (January 2000). "Cytosolic tyrosine dephosphorylation of STAT5. Potential role of SHP-2 in STAT5 regulation". The Journal of Biological Chemistry. 275 (1): 599–604. doi:10.1074/jbc.275.1.599. PMID 10617656.
  19. ↑ Chiang GG, Sefton BM (June 2001). "Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase". The Journal of Biological Chemistry. 276 (25): 23173–8. doi:10.1074/jbc.M101219200. PMID 11294838.
  20. ↑ Lorenz U, Ravichandran KS, Pei D, Walsh CT, Burakoff SJ, Neel BG (March 1994). "Lck-dependent tyrosyl phosphorylation of the phosphotyrosine phosphatase SH-PTP1 in murine T cells". Molecular and Cellular Biology. 14 (3): 1824–34. doi:10.1128/mcb.14.3.1824. PMC 358540. PMID 8114715.
  21. ↑ Koretzky GA, Kohmetscher M, Ross S (April 1993). "CD45-associated kinase activity requires lck but not T cell receptor expression in the Jurkat T cell line". The Journal of Biological Chemistry. 268 (12): 8958–64. PMID 8473339.
  22. ↑ Ng DH, Watts JD, Aebersold R, Johnson P (January 1996). "Demonstration of a direct interaction between p56lck and the cytoplasmic domain of CD45 in vitro". The Journal of Biological Chemistry. 271 (3): 1295–300. doi:10.1074/jbc.271.3.1295. PMID 8576115.
  23. ↑ Gorska MM, Stafford SJ, Cen O, Sur S, Alam R (February 2004). "Unc119, a novel activator of Lck/Fyn, is essential for T cell activation". The Journal of Experimental Medicine. 199 (3): 369–79. doi:10.1084/jem.20030589. PMC 2211793. PMID 14757743.
  24. ↑ 24.0 24.1 Thome M, Duplay P, Guttinger M, Acuto O (June 1995). "Syk and ZAP-70 mediate recruitment of p56lck/CD4 to the activated T cell receptor/CD3/zeta complex". The Journal of Experimental Medicine. 181 (6): 1997–2006. doi:10.1084/jem.181.6.1997. PMC 2192070. PMID 7539035.
  25. ↑ Oda H, Kumar S, Howley PM (August 1999). "Regulation of the Src family tyrosine kinase Blk through E6AP-mediated ubiquitination". Proceedings of the National Academy of Sciences of the United States of America. 96 (17): 9557–62. doi:10.1073/pnas.96.17.9557. PMC 22247. PMID 10449731.
  26. ↑ Pelosi M, Di Bartolo V, Mounier V, Mège D, Pascussi JM, Dufour E, Blondel A, Acuto O (May 1999). "Tyrosine 319 in the interdomain B of ZAP-70 is a binding site for the Src homology 2 domain of Lck". The Journal of Biological Chemistry. 274 (20): 14229–37. doi:10.1074/jbc.274.20.14229. PMID 10318843.

Further reading

External links

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