MAP2K4: Difference between revisions

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{{main|Mitogen-activated protein kinase kinase}}
{{main|Mitogen-activated protein kinase kinase}}
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{{Infobox_gene}}
{{GNF_Protein_box
'''Dual specificity mitogen-activated protein kinase kinase 4''' is an [[enzyme]] that in humans is encoded by the ''MAP2K4'' [[gene]].<ref name="pmid7716521">{{cite journal |vauthors=Lin A, Minden A, Martinetto H, Claret FX, Lange-Carter C, Mercurio F, Johnson GL, Karin M | title = Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2 | journal = Science | volume = 268 | issue = 5208 | pages = 286–90 |date=May 1995 | pmid = 7716521 | pmc =  | doi =10.1126/science.7716521 }}</ref>
| image = 
| image_source = 
| PDB =
| Name = Mitogen-activated protein kinase kinase 4
| HGNCid = 6844
| Symbol = MAP2K4
| AltSymbols =; JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4; SEK1; SERK1
| OMIM = 601335
| ECnumber = 
| Homologene = 48159
| MGIid = 1346869
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0004674 |text = protein serine/threonine kinase activity}} {{GNF_GO|id=GO:0004713 |text = protein-tyrosine kinase activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0016740 |text = transferase activity}}
| Component =  
  | Process = {{GNF_GO|id=GO:0006468 |text = protein amino acid phosphorylation}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007254 |text = JNK cascade}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 6416
    | Hs_Ensembl = ENSG00000065559
    | Hs_RefseqProtein = NP_003001
    | Hs_RefseqmRNA = NM_003010
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 17
    | Hs_GenLoc_start = 11864866
    | Hs_GenLoc_end = 11987865
    | Hs_Uniprot = P45985
    | Mm_EntrezGene = 26398
    | Mm_Ensembl = ENSMUSG00000033352
    | Mm_RefseqmRNA = NM_009157
    | Mm_RefseqProtein = NP_033183
    | Mm_GenLoc_db =   
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 65504439
    | Mm_GenLoc_end = 65604492
    | Mm_Uniprot = Q543X6
  }}
}}
'''Mitogen-activated protein kinase kinase 4''', also known as '''MAP2K4''', is a human [[gene]].


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{{PBB_Summary
{{PBB_Summary
| section_title =  
| section_title =  
| summary_text = This gene encodes a dual specificity protein kinase that belongs to the Ser/Thr protein kinase family. This kinase is a direct activator of MAP kinases in response to various environmental stresses or mitogenic stimuli. It has been shown to activate MAPK8/JNK1, MAPK9/JNK2, and MAPK14/p38, but not MAPK1/ERK2 or MAPK3/ERK1. This kinase is phosphorylated, and thus activated by MAP3K1/MEKK. The knockout studies in mice suggested the roles of this kinase in mediating survival signal in T cell development, as well as in the organogenesis of liver.<ref>{{cite web | title = Entrez Gene: MAP2K4 mitogen-activated protein kinase kinase 4| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6416| accessdate = }}</ref>
| summary_text = This gene encodes a dual specificity protein kinase that belongs to the [[Serine/threonine-specific protein kinase|Ser/Thr protein kinase family]]. This kinase is a direct activator of MAP kinases in response to various environmental stresses or mitogenic stimuli. It has been shown to activate MAPK8/JNK1, MAPK9/JNK2, and MAPK14/p38, but not MAPK1/ERK2 or MAPK3/ERK1. This kinase is phosphorylated, and thus activated by MAP3K1/MEKK. The knockout studies in mice suggested the roles of this kinase in mediating survival signal in T cell development, as well as in the organogenesis of liver.<ref>{{cite web | title = Entrez Gene: MAP2K4 mitogen-activated protein kinase kinase 4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6416| accessdate = }}</ref>
}}
}}
==Interactions==
MAP2K4 has been shown to [[Protein-protein interaction|interact]] with [[FLNC (gene)|FLNC]],<ref name=pmid9006895>{{cite journal |last=Marti |first=A |authorlink= |author2=Luo Z |author3=Cunningham C |author4=Ohta Y |author5=Hartwig J |author6=Stossel T P |author7=Kyriakis J M |author8=Avruch J  |date=January 1997  |title=Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells |journal=J. Biol. Chem. |volume=272 |issue=5 |pages=2620–8 |publisher= |location = UNITED STATES| issn = 0021-9258| pmid = 9006895 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |doi=10.1074/jbc.272.5.2620 }}</ref> [[MAPK8]],<ref name=pmid12391307>{{cite journal |last=Lee |first=Clement M |authorlink= |author2=Onésime Djamila |author3=Reddy C Damodara |author4=Dhanasekaran N |author5=Reddy E Premkumar  |date=October 2002  |title=JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors |journal=[[PNAS|Proc. Natl. Acad. Sci. U.S.A.]] |volume=99 |issue=22 |pages=14189–94 |publisher= |location = United States| issn = 0027-8424| pmid = 12391307 |doi = 10.1073/pnas.232310199 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |pmc=137859 }}</ref><ref name=pmid11707464>{{cite journal |last=Park |first=Hee-Sae |authorlink= |author2=Kim Mi-Sung |author3=Huh Sung-Ho |author4=Park Jihyun |author5=Chung Jongkyeong |author6=Kang Sang Sun |author7=Choi Eui-Ju  |date=January 2002  |title=Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation |journal=J. Biol. Chem. |volume=277 |issue=4 |pages=2573–8 |publisher= |location = United States| issn = 0021-9258| pmid = 11707464 |doi = 10.1074/jbc.M110299200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref><ref name=pmid11279118>{{cite journal |last=Chen |first=Z |authorlink= |author2=Cobb M H  |date=May 2001 |title=Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2 |journal=J. Biol. Chem. |volume=276 |issue=19 |pages=16070–5 |publisher= |location = United States| issn = 0021-9258| pmid = 11279118 |doi = 10.1074/jbc.M100681200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref><ref name=pmid9207092>{{cite journal |last=Tournier |first=C |authorlink= |author2=Whitmarsh A J |author3=Cavanagh J |author4=Barrett T |author5=Davis R J  |date=July 1997  |title=Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun  NH2-terminal kinase |journal=[[PNAS|Proc. Natl. Acad. Sci. U.S.A.]] |volume=94 |issue=14 |pages=7337–42 |publisher= |location = UNITED STATES| issn = 0027-8424| pmid = 9207092 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |doi=10.1073/pnas.94.14.7337 |pmc=23822 }}</ref><ref name=pmid10713157>{{cite journal |last=Cheng |first=J |authorlink= |author2=Yang J |author3=Xia Y |author4=Karin M |author5=Su B  |date=April 2000  |title=Synergistic interaction of MEK kinase 2, c-Jun  N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation |journal=Mol. Cell. Biol. |volume=20 |issue=7 |pages=2334–42 |publisher= |location = UNITED STATES| issn = 0270-7306| pmid = 10713157 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |doi=10.1128/MCB.20.7.2334-2342.2000 |pmc=85399 }}</ref> [[MAPK8IP3]]<ref name=pmid10523642>{{cite journal |last=Ito |first=M |authorlink= |author2=Yoshioka K |author3=Akechi M |author4=Yamashita S |author5=Takamatsu N |author6=Sugiyama K |author7=Hibi M |author8=Nakabeppu Y |author9=Shiba T |author10=Yamamoto K I  |date=November 1999  |title=JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway |journal=Mol. Cell. Biol. |volume=19 |issue=11 |pages=7539–48 |publisher= |location = UNITED STATES| issn = 0270-7306| pmid = 10523642 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |pmc=84763 | doi=10.1128/mcb.19.11.7539}}</ref><ref name=pmid12189133>{{cite journal |last=Matsuura |first=Hiroshi |authorlink= |author2=Nishitoh Hideki |author3=Takeda Kohsuke |author4=Matsuzawa Atsushi |author5=Amagasa Teruo |author6=Ito Michihiko |author7=Yoshioka Katsuji |author8=Ichijo Hidenori  |date=October 2002  |title=Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascade |journal=J. Biol. Chem. |volume=277 |issue=43 |pages=40703–9 |publisher= |location = United States| issn = 0021-9258| pmid = 12189133 |doi = 10.1074/jbc.M202004200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref> and [[AKT1]].<ref name=pmid11707464/>


==References==
==References==
{{reflist|2}}
{{reflist}}


==Further reading==
==Further reading==
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{{PBB_Further_reading  
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| citations =  
| citations =  
*{{cite journal  | author=Lin A, Minden A, Martinetto H, ''et al.'' |title=Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2. |journal=Science |volume=268 |issue= 5208 |pages= 286-90 |year= 1995 |pmid= 7716521 |doi=  }}
*{{cite journal  | author=Dérijard B |title=Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms |journal=Science |volume=267 |issue= 5198 |pages= 682–5 |year= 1995 |pmid= 7839144 |doi=10.1126/science.7839144 |name-list-format=vanc| author2=Raingeaud J | author3=Barrett T | display-authors=| last4=Wu  | first4=I.  | last5=Han  | first5=| last6=Ulevitch  | first6=R.  | last7=Davis  | first7=R. }}
*{{cite journal  | author=Dérijard B, Raingeaud J, Barrett T, ''et al.'' |title=Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. |journal=Science |volume=267 |issue= 5198 |pages= 682-5 |year= 1995 |pmid= 7839144 |doi=  }}
*{{cite journal  | author=Yan M |title=Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1 |journal=Nature |volume=372 |issue= 6508 |pages= 798–800 |year= 1995 |pmid= 7997270 |doi= 10.1038/372798a0 |name-list-format=vanc| author2=Dai T  | author3=Deak JC  | display-authors=3  | last4=Kyriakis  | first4=JM  | last5=Zon  | first5=LI  | last6=Woodgett  | first6=JR  | last7=Templeton  | first7=DJ }}
*{{cite journal  | author=Yan M, Dai T, Deak JC, ''et al.'' |title=Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1. |journal=Nature |volume=372 |issue= 6508 |pages= 798-800 |year= 1995 |pmid= 7997270 |doi= }}
*{{cite journal  | author=Salmeron A |title=Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase |journal=EMBO J. |volume=15 |issue= 4 |pages= 817–26 |year= 1996 |pmid= 8631303 |doi= | pmc=450280  |name-list-format=vanc| author2=Ahmad TB  | author3=Carlile GW  | display-authors=3  | last4=Pappin  | first4=| last5=Narsimhan  | first5=RP  | last6=Ley  | first6=SC  }}
*{{cite journal  | author=Salmeron A, Ahmad TB, Carlile GW, ''et al.'' |title=Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase. |journal=EMBO J. |volume=15 |issue= 4 |pages= 817-26 |year= 1996 |pmid= 8631303 |doi=  }}
*{{cite journal  | author=Gale NW |title=Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis |journal=Neuron |volume=17 |issue= 1 |pages= 9–19 |year= 1996 |pmid= 8755474 |doi=10.1016/S0896-6273(00)80276-7 |name-list-format=vanc| author2=Holland SJ  | author3=Valenzuela DM  | display-authors=3  | last4=Flenniken  | first4=Ann  | last5=Pan  | first5=Li  | last6=Ryan  | first6=Terrence E  | last7=Henkemeyer  | first7=Mark  | last8=Strebhardt  | first8=Klaus  | last9=Hirai  | first9=Hisamaru }}
*{{cite journal  | author=Gale NW, Holland SJ, Valenzuela DM, ''et al.'' |title=Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis. |journal=Neuron |volume=17 |issue= 1 |pages= 9-19 |year= 1996 |pmid= 8755474 |doi= }}
*{{cite journal  | author=White RA |title=The gene encoding protein kinase SEK1 maps to mouse chromosome 11 and human chromosome 17 |journal=Genomics |volume=34 |issue= 3 |pages= 430–2 |year= 1996 |pmid= 8786147 |doi= 10.1006/geno.1996.0309 |name-list-format=vanc| author2=Hughes RT | author3=Adkison LR  | display-authors=3  | last4=Bruns  | first4=G  | last5=Zon  | first5=LI }}
*{{cite journal  | author=White RA, Hughes RT, Adkison LR, ''et al.'' |title=The gene encoding protein kinase SEK1 maps to mouse chromosome 11 and human chromosome 17. |journal=Genomics |volume=34 |issue= 3 |pages= 430-2 |year= 1996 |pmid= 8786147 |doi= 10.1006/geno.1996.0309 }}
*{{cite journal  | author=Nishina H |title=Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3 |journal=Nature |volume=385 |issue= 6614 |pages= 350–3 |year= 1997 |pmid= 9002521 |doi= 10.1038/385350a0 |name-list-format=vanc| author2=Fischer KD | author3=Radvanyi L  | display-authors=3  | last4=Shahinian  | first4=Arda  | last5=Hakem  | first5=Razqallah  | last6=Rubie  | first6=Elizabeth A.  | last7=Bernstein | first7=Alan  | last8=Mak  | first8=Tak W.  | last9=Woodgett  | first9=James R. }}
*{{cite journal  | author=Nishina H, Fischer KD, Radvanyi L, ''et al.'' |title=Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3. |journal=Nature |volume=385 |issue= 6614 |pages= 350-3 |year= 1997 |pmid= 9002521 |doi= 10.1038/385350a0 }}
*{{cite journal  | author=Marti A |title=Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells |journal=J. Biol. Chem. |volume=272 |issue= 5 |pages= 2620–8 |year= 1997 |pmid= 9006895 |doi=10.1074/jbc.272.5.2620 |name-list-format=vanc| author2=Luo Z | author3=Cunningham C  | display-authors=3  | last4=Ohta  | first4=Y  | last5=Hartwig  | first5=J | last6=Stossel  | first6=TP  | last7=Kyriakis  | first7=JM  | last8=Avruch  | first8=J }}
*{{cite journal | author=Marti A, Luo Z, Cunningham C, ''et al.'' |title=Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells. |journal=J. Biol. Chem. |volume=272 |issue= 5 |pages= 2620-8 |year= 1997 |pmid= 9006895 |doi=  }}
*{{cite journal  |vauthors=Deacon K, Blank JL |title=Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun  NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo |journal=J. Biol. Chem. |volume=272 |issue= 22 |pages= 14489–96 |year= 1997 |pmid= 9162092 |doi=10.1074/jbc.272.22.14489 }}
*{{cite journal  | author=Deacon K, Blank JL |title=Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo. |journal=J. Biol. Chem. |volume=272 |issue= 22 |pages= 14489-96 |year= 1997 |pmid= 9162092 |doi=  }}
*{{cite journal  | author=Hirai S |title=MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of c-Jun  N-terminal kinase/stress-activated protein kinase |journal=J. Biol. Chem. |volume=272 |issue= 24 |pages= 15167–73 |year= 1997 |pmid= 9182538 |doi=10.1074/jbc.272.24.15167 |name-list-format=vanc| author2=Katoh M  | author3=Terada M  | display-authors=| last4=Kyriakis  | first4=JM  | last5=Zon  | first5=LI  | last6=Rana  | first6=A  | last7=Avruch  | first7=| last8=Ohno  | first8=S }}
*{{cite journal | author=Hirai S, Katoh M, Terada M, ''et al.'' |title=MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of c-Jun N-terminal kinase/stress-activated protein kinase. |journal=J. Biol. Chem. |volume=272 |issue= 24 |pages= 15167-73 |year= 1997 |pmid= 9182538 |doi=  }}
*{{cite journal  | author=Teng DH |title=Human mitogen-activated protein kinase kinase 4 as a candidate tumor suppressor |journal=Cancer Res. |volume=57 |issue= 19 |pages= 4177–82 |year= 1997 |pmid= 9331070 |doi=  |name-list-format=vanc| author2=Perry WL  | author3=Hogan JK  | display-authors=3  | last4=Baumgard  | first4=M  | last5=Bell  | first5=R  | last6=Berry  | first6=S  | last7=Davis  | first7=T  | last8=Frank  | first8=D  | last9=Frye  | first9=C  }}
*{{cite journal | author=Teng DH, Perry WL, Hogan JK, ''et al.'' |title=Human mitogen-activated protein kinase kinase 4 as a candidate tumor suppressor. |journal=Cancer Res. |volume=57 |issue= 19 |pages= 4177-82 |year= 1997 |pmid= 9331070 |doi}}
*{{cite journal  |vauthors=Xu S, Cobb MH |title=MEKK1 binds directly to the c-Jun  N-terminal kinases/stress-activated protein kinases |journal=J. Biol. Chem. |volume=272 |issue= 51 |pages= 32056–60 |year= 1998 |pmid= 9405400 |doi=10.1074/jbc.272.51.32056  }}
*{{cite journal  | author=Xu S, Cobb MH |title=MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases. |journal=J. Biol. Chem. |volume=272 |issue= 51 |pages= 32056-60 |year= 1998 |pmid= 9405400 |doi=  }}
*{{cite journal  | author=Guan Z |title=Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway |journal=J. Biol. Chem. |volume=273 |issue= 21 |pages= 12901–8 |year= 1998 |pmid= 9582321 |doi=10.1074/jbc.273.21.12901  |name-list-format=vanc| author2=Buckman SY  | author3=Pentland AP  | display-authors=3  | last4=Templeton  | first4=DJ  | last5=Morrison  | first5=AR  }}
*{{cite journal | author=Guan Z, Buckman SY, Pentland AP, ''et al.'' |title=Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway. |journal=J. Biol. Chem. |volume=273 |issue= 21 |pages= 12901-8 |year= 1998 |pmid= 9582321 |doi=  }}
*{{cite journal  | author=Su GH |title=Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene |journal=Cancer Res. |volume=58 |issue= 11 |pages= 2339–42 |year= 1998 |pmid= 9622070 |doi=  |name-list-format=vanc| author2=Hilgers W  | author3=Shekher MC  | display-authors=3  | last4=Tang  | first4=DJ  | last5=Yeo  | first5=CJ  | last6=Hruban  | first6=RH  | last7=Kern  | first7=SE  }}
*{{cite journal  | author=Su GH, Hilgers W, Shekher MC, ''et al.'' |title=Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene. |journal=Cancer Res. |volume=58 |issue= 11 |pages= 2339-42 |year= 1998 |pmid= 9622070 |doi=  }}
*{{cite journal  | author=Yang J |title=Molecular cloning and characterization of a human protein kinase that specifically activates c-Jun  N-terminal kinase |journal=Gene |volume=212 |issue= 1 |pages= 95–102 |year= 1998 |pmid= 9661668 |doi=10.1016/S0378-1119(98)00158-9  |name-list-format=vanc| author2=New L  | author3=Jiang Y  | display-authors=3  | last4=Han  | first4=J  | last5=Su  | first5=B  }}
*{{cite journal | author=Yang J, New L, Jiang Y, ''et al.'' |title=Molecular cloning and characterization of a human protein kinase that specifically activates c-Jun N-terminal kinase. |journal=Gene |volume=212 |issue= 1 |pages= 95-102 |year= 1998 |pmid= 9661668 |doi=  }}
*{{cite journal  | author=Widegren U |title=Divergent effects of exercise on metabolic and mitogenic signaling pathways in human skeletal muscle |journal=FASEB J. |volume=12 |issue= 13 |pages= 1379–89 |year= 1998 |pmid= 9761781 |doi=  |name-list-format=vanc| author2=Jiang XJ  | author3=Krook A  | display-authors=3  | last4=Chibalin  | first4=AV  | last5=Björnholm  | first5=M  | last6=Tally  | first6=M  | last7=Roth  | first7=RA  | last8=Henriksson  | first8=J  | last9=Wallberg-Henriksson  | first9=H  }}
*{{cite journal  | author=Widegren U, Jiang XJ, Krook A, ''et al.'' |title=Divergent effects of exercise on metabolic and mitogenic signaling pathways in human skeletal muscle. |journal=FASEB J. |volume=12 |issue= 13 |pages= 1379-89 |year= 1998 |pmid= 9761781 |doi= }}
*{{cite journal  | author=Xia Y |title=JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension |journal=Genes Dev. |volume=12 |issue= 21 |pages= 3369–81 |year= 1998 |pmid= 9808624 |doi=10.1101/gad.12.21.3369  | pmc=317229  |name-list-format=vanc| author2=Wu Z  | author3=Su B  | display-authors=3  | last4=Murray  | first4=B.  | last5=Karin  | first5=M.  }}
*{{cite journal | author=Xia Y, Wu Z, Su B, ''et al.'' |title=JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension. |journal=Genes Dev. |volume=12 |issue= 21 |pages= 3369-81 |year= 1998 |pmid= 9808624 |doi=  }}
*{{cite journal  |vauthors=Chan-Hui PY, Weaver R |title=Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase cascades |journal=Biochem. J. |volume=336 |issue=  3|pages= 599–609 |year= 1999 |pmid= 9841871 |doi=  10.1042/bj3360599| pmc=1219910  }}
*{{cite journal  | author=Chan-Hui PY, Weaver R |title=Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase cascades. |journal=Biochem. J. |volume=336 ( Pt 3) |issue= |pages= 599-609 |year= 1999 |pmid= 9841871 |doi= }}
*{{cite journal  | author=Merritt SE |title=The mixed lineage kinase DLK utilizes MKK7 and not MKK4 as substrate |journal=J. Biol. Chem. |volume=274 |issue= 15 |pages= 10195–202 |year= 1999 |pmid= 10187804 |doi=10.1074/jbc.274.15.10195  |name-list-format=vanc| author2=Mata M  | author3=Nihalani D  | display-authors=3  | last4=Zhu  | first4=C  | last5=Hu  | first5=X  | last6=Holzman  | first6=LB  }}
*{{cite journal | author=Merritt SE, Mata M, Nihalani D, ''et al.'' |title=The mixed lineage kinase DLK utilizes MKK7 and not MKK4 as substrate. |journal=J. Biol. Chem. |volume=274 |issue= 15 |pages= 10195-202 |year= 1999 |pmid= 10187804 |doi=  }}
*{{cite journal  | author=Orth K |title=Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector |journal=Science |volume=285 |issue= 5435 |pages= 1920–3 |year= 1999 |pmid= 10489373 |doi=10.1126/science.285.5435.1920  |name-list-format=vanc| author2=Palmer LE  | author3=Bao ZQ  | display-authors=3  | last4=Stewart  | first4=S  | last5=Rudolph  | first5=AE  | last6=Bliska  | first6=JB  | last7=Dixon | first7=JE }}
*{{cite journal | author=Orth K, Palmer LE, Bao ZQ, ''et al.'' |title=Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector. |journal=Science |volume=285 |issue= 5435 |pages= 1920-3 |year= 1999 |pmid= 10489373 |doi=  }}
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[[Category:EC 2.7.12]]

Revision as of 06:05, 4 September 2017

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Identifiers
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Dual specificity mitogen-activated protein kinase kinase 4 is an enzyme that in humans is encoded by the MAP2K4 gene.[1]

This gene encodes a dual specificity protein kinase that belongs to the Ser/Thr protein kinase family. This kinase is a direct activator of MAP kinases in response to various environmental stresses or mitogenic stimuli. It has been shown to activate MAPK8/JNK1, MAPK9/JNK2, and MAPK14/p38, but not MAPK1/ERK2 or MAPK3/ERK1. This kinase is phosphorylated, and thus activated by MAP3K1/MEKK. The knockout studies in mice suggested the roles of this kinase in mediating survival signal in T cell development, as well as in the organogenesis of liver.[2]

Interactions

MAP2K4 has been shown to interact with FLNC,[3] MAPK8,[4][5][6][7][8] MAPK8IP3[9][10] and AKT1.[5]

References

  1. Lin A, Minden A, Martinetto H, Claret FX, Lange-Carter C, Mercurio F, Johnson GL, Karin M (May 1995). "Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2". Science. 268 (5208): 286–90. doi:10.1126/science.7716521. PMID 7716521.
  2. "Entrez Gene: MAP2K4 mitogen-activated protein kinase kinase 4".
  3. Marti, A; Luo Z; Cunningham C; Ohta Y; Hartwig J; Stossel T P; Kyriakis J M; Avruch J (January 1997). "Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells". J. Biol. Chem. UNITED STATES. 272 (5): 2620–8. doi:10.1074/jbc.272.5.2620. ISSN 0021-9258. PMID 9006895.
  4. Lee, Clement M; Onésime Djamila; Reddy C Damodara; Dhanasekaran N; Reddy E Premkumar (October 2002). "JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors". Proc. Natl. Acad. Sci. U.S.A. United States. 99 (22): 14189–94. doi:10.1073/pnas.232310199. ISSN 0027-8424. PMC 137859. PMID 12391307.
  5. 5.0 5.1 Park, Hee-Sae; Kim Mi-Sung; Huh Sung-Ho; Park Jihyun; Chung Jongkyeong; Kang Sang Sun; Choi Eui-Ju (January 2002). "Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation". J. Biol. Chem. United States. 277 (4): 2573–8. doi:10.1074/jbc.M110299200. ISSN 0021-9258. PMID 11707464.
  6. Chen, Z; Cobb M H (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. United States. 276 (19): 16070–5. doi:10.1074/jbc.M100681200. ISSN 0021-9258. PMID 11279118.
  7. Tournier, C; Whitmarsh A J; Cavanagh J; Barrett T; Davis R J (July 1997). "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. UNITED STATES. 94 (14): 7337–42. doi:10.1073/pnas.94.14.7337. ISSN 0027-8424. PMC 23822. PMID 9207092.
  8. Cheng, J; Yang J; Xia Y; Karin M; Su B (April 2000). "Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation". Mol. Cell. Biol. UNITED STATES. 20 (7): 2334–42. doi:10.1128/MCB.20.7.2334-2342.2000. ISSN 0270-7306. PMC 85399. PMID 10713157.
  9. Ito, M; Yoshioka K; Akechi M; Yamashita S; Takamatsu N; Sugiyama K; Hibi M; Nakabeppu Y; Shiba T; Yamamoto K I (November 1999). "JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway". Mol. Cell. Biol. UNITED STATES. 19 (11): 7539–48. doi:10.1128/mcb.19.11.7539. ISSN 0270-7306. PMC 84763. PMID 10523642.
  10. Matsuura, Hiroshi; Nishitoh Hideki; Takeda Kohsuke; Matsuzawa Atsushi; Amagasa Teruo; Ito Michihiko; Yoshioka Katsuji; Ichijo Hidenori (October 2002). "Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascade". J. Biol. Chem. United States. 277 (43): 40703–9. doi:10.1074/jbc.M202004200. ISSN 0021-9258. PMID 12189133.

Further reading