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{{Infobox_gene}}
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'''Growth factor receptor-bound protein 7''', also known as '''GRB7''', is a [[protein]] that in humans is encoded by the ''GRB7'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: GRB7 growth factor receptor-bound protein 7| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2886| accessdate = }}</ref><ref name="pmid9710451">{{cite journal | vauthors = Tanaka S, Mori M, Akiyoshi T, Tanaka Y, Mafune K, Wands JR, Sugimachi K | title = A novel variant of human Grb7 is associated with invasive esophageal carcinoma | journal = The Journal of Clinical Investigation | volume = 102 | issue = 4 | pages = 821–7 | date = Aug 1998 | pmid = 9710451 | pmc = 508945 | doi = 10.1172/JCI2921 }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_GRB7_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1mw4.
| PDB = {{PDB2|1mw4}}, {{PDB2|1wgr}}
| Name = Growth factor receptor-bound protein 7
| HGNCid = 4567
| Symbol = GRB7
| AltSymbols =;
| OMIM = 601522
| ECnumber = 
| Homologene = 3881
| MGIid = 102683
| GeneAtlas_image1 = PBB_GE_GRB7_210761_s_at_tn.png
| Function = {{GNF_GO|id=GO:0005070 |text = SH3/SH2 adaptor activity}}
| Component =
| Process = {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007173 |text = epidermal growth factor receptor signaling pathway}} {{GNF_GO|id=GO:0007242 |text = intracellular signaling cascade}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 2886
    | Hs_Ensembl = ENSG00000141738
    | Hs_RefseqProtein = NP_001025173
    | Hs_RefseqmRNA = NM_001030002
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 17
    | Hs_GenLoc_start = 35147713
    | Hs_GenLoc_end = 35157061
    | Hs_Uniprot = Q14451
    | Mm_EntrezGene = 14786
    | Mm_Ensembl = ENSMUSG00000019312
    | Mm_RefseqmRNA = NM_010346
    | Mm_RefseqProtein = NP_034476
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 98262929
    | Mm_GenLoc_end = 98271460
    | Mm_Uniprot = Q3TH55
  }}
}}


'''Growth factor receptor-bound protein 7''', also known as '''GRB7''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: GRB7 growth factor receptor-bound protein 7| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2886| accessdate = }}</ref>
The product of this gene belongs to a small family of [[Signal transducing adaptor protein|adaptor protein]]s that are known to interact with a number of [[receptor tyrosine kinase]]s and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with [[epidermal growth factor receptor]] (EGFR) and [[Eph receptor|ephrin receptors]]. The protein plays a role in the [[integrin]] signaling pathway and cell migration by binding with [[PTK2|focal adhesion kinase]] (FAK). [[Alternative splicing]] results in multiple transcript variants encoding different [[protein isoform|isoforms]], although the full-length natures of only two of the variants have been determined to date.<ref name="entrez" />
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
 
{{PBB_Summary
== Clinical significance ==
| section_title =
 
| summary_text = The product of this gene belongs to a small family of adapter proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with epidermal growth factor receptor (EGFR) and ephrin receptors. The protein plays a role in the integrin signaling pathway and cell migration by binding with focal adhesion kinase (FAK). Alternative splicing results in multiple transcript variants encoding different isoforms, although the full-length natures of only two of the variants have been determined to date.<ref name="entrez">{{cite web | title = Entrez Gene: GRB7 growth factor receptor-bound protein 7| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2886| accessdate = }}</ref>
GRB7 is an SH2-domain adaptor [[protein]] that binds to [[receptor tyrosine kinase]]s and provides the intra-cellular direct link to the [[Ras (protein)|Ras]] [[proto-oncogene]].
}}
Human GRB7 is located on the long arm of [[Chromosome 17 (human)|chromosome 17]], next to the ERBB2 (alias [[HER2/neu]]) proto-oncogene.
GRB7 is an SH2-domain adaptor [[protein]] that binds to [[Receptor-tyrosine kinases]] and provides the intra-cellular direct link to the [[Ras]] [[proto-oncogene]].
Human [[GRB7]] is located on the long arm of [[Chromosome 17 (human)|chromosome 17]], next to the [[ERBB2]] (alias her2/neu) proto-oncogene.


These two genes are commonly co-amplified (present in excess copies) in [[breast cancer]]s.
These two genes are commonly co-amplified (present in excess copies) in [[breast cancer]]s.
[[GRB7]], thought to be involved in migration {{Fact|date=September 2007}}, is well known to be over-expressed in [[testicular germ cell tumor]]s, [[esophagous cancer]]s, and [[gastric cancer]]s.
GRB7 thought to be involved in migration {{Citation needed|date=September 2007}}, is well known to be over-expressed in testicular [[germ cell tumor]]s, [[esophageal cancer]]s, and [[stomach cancer|gastric cancer]]s.
 
== Interactions ==
 
GRB7 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[EPH receptor B1]],<ref name = pmid12223469>{{cite journal | vauthors = Han DC, Shen TL, Miao H, Wang B, Guan JL | title = EphB1 associates with Grb7 and regulates cell migration | journal = The Journal of Biological Chemistry | volume = 277 | issue = 47 | pages = 45655–61 | date = Nov 2002 | pmid = 12223469 | doi = 10.1074/jbc.M203165200 }}</ref>
* [[Insulin receptor]],<ref name = pmid10803466>{{cite journal | vauthors = Kasus-Jacobi A, Béréziat V, Perdereau D, Girard J, Burnol AF | title = Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2 | journal = Oncogene | volume = 19 | issue = 16 | pages = 2052–9 | date = Apr 2000 | pmid = 10803466 | doi = 10.1038/sj.onc.1203469 }}</ref>
* [[PTK2]],<ref name = pmid10446223>{{cite journal | vauthors = Han DC, Guan JL | title = Association of focal adhesion kinase with Grb7 and its role in cell migration | journal = The Journal of Biological Chemistry | volume = 274 | issue = 34 | pages = 24425–30 | date = Aug 1999 | pmid = 10446223 | doi =  10.1074/jbc.274.34.24425}}</ref>
* [[RET proto-oncogene]],<ref name = pmid8631863>{{cite journal | vauthors = Pandey A, Liu X, Dixon JE, Di Fiore PP, Dixit VM | title = Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7 | journal = The Journal of Biological Chemistry | volume = 271 | issue = 18 | pages = 10607–10 | date = May 1996 | pmid = 8631863 | doi =  10.1074/jbc.271.18.10607}}</ref>  and
* [[Rnd1]]<ref name = pmid10664463>{{cite journal | vauthors = Vayssière B, Zalcman G, Mahé Y, Mirey G, Ligensa T, Weidner KM, Chardin P, Camonis J | title = Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho family | journal = FEBS Letters | volume = 467 | issue = 1 | pages = 91–6 | date = Feb 2000 | pmid = 10664463 | doi =  10.1016/s0014-5793(99)01530-6}}</ref>
{{Div col end}}
 
== Model organisms ==
 
[[Model organism]]s have been used in the study of GRB7 function. A conditional [[knockout mouse]] line called ''Grb7<sup>tm1b(EUCOMM)Wtsi</sup>'' was generated at the [[Wellcome Trust Sanger Institute]].<ref name="mgp_reference">{{cite journal |title=The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice |author=Gerdin AK |year=2010 |journal=Acta Ophthalmologica|volume=88 |pages=925–7|doi=10.1111/j.1755-3768.2010.4142.x }}</ref> Male and female animals underwent a standardized [[phenotypic screen]]<ref name="IMPCsearch_ref">{{cite web |url=http://www.mousephenotype.org/data/search?q=Grb7#fq=*:*&facet=gene |title=International Mouse Phenotyping Consortium}}</ref> to determine the effects of deletion.<ref name="pmid21677750">{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = Jun 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = Jun 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = Jan 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref><ref name="pmid23870131">{{cite journal | vauthors = White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP | title = Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes | journal = Cell | volume = 154 | issue = 2 | pages = 452–64 | date = Jul 2013 | pmid = 23870131 | pmc = 3717207 | doi = 10.1016/j.cell.2013.06.022 }}</ref> Additional screens performed:  - In-depth immunological phenotyping<ref name="iii_ref">{{cite web |url= http://www.immunophenotyping.org/data/search?keys=Grb7&field_gene_construct_tid=All |title=Infection and Immunity Immunophenotyping (3i) Consortium}}</ref>
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: left;" |
|+ ''Grb7'' knockout mouse phenotype
|-
! Characteristic!! Phenotype
|-
| colspan=2; style="text-align: center;" | All data available at.<ref name="IMPCsearch_ref"/><ref name="iii_ref" />
 
|-
| Peripheral blood leukocytes 6 Weeks || bgcolor="#488ED3"|Normal
 
|-
| ''[[Haematology]]'' 6 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Homozygous viability at P14 || bgcolor="#488ED3"|Normal
 
|-
| Homozygous Fertility || bgcolor="#488ED3"|Normal
 
|-
| Body weight || bgcolor="#488ED3"|Normal
 
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
 
|-
| Grip strength || bgcolor="#488ED3"|Normal
 
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
 
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
 
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
 
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
 
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
 
|-
| Eye morphology || bgcolor="#488ED3"|Normal
 
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
 
|-
| ''[[Haematology]]'' 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Peripheral blood leukocytes 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Heart weight || bgcolor="#488ED3"|Normal
 
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal
 
|-
| Cytotoxic T Cell Function || bgcolor="#488ED3"|Normal
 
|-
| Spleen Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Mesenteric Lymph Node Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Bone Marrow Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Epidermal Immune Composition || bgcolor="#488ED3"|Normal
 
|-
| Trichuris Challenge || bgcolor="#488ED3"|Normal
 
|-
|}
{{clear|left}}
 
== References ==
{{reflist|33em}}


==References==
== Further reading ==
{{reflist|2}}
{{refbegin|33em}}
==Further reading==
* {{cite journal | vauthors = Han DC, Shen TL, Guan JL | title = The Grb7 family proteins: structure, interactions with other signaling molecules and potential cellular functions | journal = Oncogene | volume = 20 | issue = 44 | pages = 6315–21 | date = Oct 2001 | pmid = 11607834 | doi = 10.1038/sj.onc.1204775 }}
{{refbegin | 2}}
* {{cite journal | vauthors = Margolis B, Silvennoinen O, Comoglio F, Roonprapunt C, Skolnik E, Ullrich A, Schlessinger J | title = High-efficiency expression/cloning of epidermal growth factor-receptor-binding proteins with Src homology 2 domains | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 19 | pages = 8894–8 | date = Oct 1992 | pmid = 1409582 | pmc = 50030 | doi = 10.1073/pnas.89.19.8894 }}
{{PBB_Further_reading
* {{cite journal | vauthors = Skotheim RI, Abeler VM, Nesland JM, Fosså SD, Holm R, Wagner U, Flørenes VA, Aass N, Kallioniemi OP, Lothe RA | title = Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays | journal = Neoplasia | volume = 5 | issue = 5 | pages = 397–404 | year = 2003 | pmid = 14670177 | pmc = 1502610 | doi = 10.1016/s1476-5586(03)80042-8 }}
| citations =
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
*{{cite journal | author=Han DC, Shen TL, Guan JL |title=The Grb7 family proteins: structure, interactions with other signaling molecules and potential cellular functions. |journal=Oncogene |volume=20 |issue= 44 |pages= 6315-21 |year= 2001 |pmid= 11607834 |doi= 10.1038/sj.onc.1204775 }}
* {{cite journal | vauthors = Pandey A, Liu X, Dixon JE, Di Fiore PP, Dixit VM | title = Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7 | journal = The Journal of Biological Chemistry | volume = 271 | issue = 18 | pages = 10607–10 | date = May 1996 | pmid = 8631863 | doi = 10.1074/jbc.271.18.10607 }}
*{{cite journal | author=Margolis B, Silvennoinen O, Comoglio F, ''et al.'' |title=High-efficiency expression/cloning of epidermal growth factor-receptor-binding proteins with Src homology 2 domains. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue= 19 |pages= 8894-8 |year= 1992 |pmid= 1409582 |doi= }}
* {{cite journal | vauthors = Yokote K, Margolis B, Heldin CH, Claesson-Welsh L | title = Grb7 is a downstream signaling component of platelet-derived growth factor alpha- and beta-receptors | journal = The Journal of Biological Chemistry | volume = 271 | issue = 48 | pages = 30942–9 | date = Nov 1996 | pmid = 8940081 | doi = 10.1074/jbc.271.48.30942 }}
*{{cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi= }}
* {{cite journal | vauthors = Tanaka S, Mori M, Akiyoshi T, Tanaka Y, Mafune K, Wands JR, Sugimachi K | title = Coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 in human advanced esophageal carcinoma | journal = Cancer Research | volume = 57 | issue = 1 | pages = 28–31 | date = Jan 1997 | pmid = 8988034 | doi =  }}
*{{cite journal | author=Pandey A, Liu X, Dixon JE, ''et al.'' |title=Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7. |journal=J. Biol. Chem. |volume=271 |issue= 18 |pages= 10607-10 |year= 1996 |pmid= 8631863 |doi= }}
* {{cite journal | vauthors = Janes PW, Lackmann M, Church WB, Sanderson GM, Sutherland RL, Daly RJ | title = Structural determinants of the interaction between the erbB2 receptor and the Src homology 2 domain of Grb7 | journal = The Journal of Biological Chemistry | volume = 272 | issue = 13 | pages = 8490–7 | date = Mar 1997 | pmid = 9079677 | doi = 10.1074/jbc.272.13.8490 }}
*{{cite journal | author=Yokote K, Margolis B, Heldin CH, Claesson-Welsh L |title=Grb7 is a downstream signaling component of platelet-derived growth factor alpha- and beta-receptors. |journal=J. Biol. Chem. |volume=271 |issue= 48 |pages= 30942-9 |year= 1997 |pmid= 8940081 |doi= }}
* {{cite journal | vauthors = Kishi T, Sasaki H, Akiyama N, Ishizuka T, Sakamoto H, Aizawa S, Sugimura T, Terada M | title = Molecular cloning of human GRB-7 co-amplified with CAB1 and c-ERBB-2 in primary gastric cancer | journal = Biochemical and Biophysical Research Communications | volume = 232 | issue = 1 | pages = 5–9 | date = Mar 1997 | pmid = 9125150 | doi = 10.1006/bbrc.1997.6218 }}
*{{cite journal | author=Tanaka S, Mori M, Akiyoshi T, ''et al.'' |title=Coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 in human advanced esophageal carcinoma. |journal=Cancer Res. |volume=57 |issue= 1 |pages= 28-31 |year= 1997 |pmid= 8988034 |doi= }}
* {{cite journal | vauthors = Dong LQ, Du H, Porter SG, Kolakowski LF, Lee AV, Mandarino LJ, Fan J, Yee D, Liu F, Mandarino J | title = Cloning, chromosome localization, expression, and characterization of an Src homology 2 and pleckstrin homology domain-containing insulin receptor binding protein hGrb10gamma | journal = The Journal of Biological Chemistry | volume = 272 | issue = 46 | pages = 29104–12 | date = Nov 1997 | pmid = 9360986 | doi = 10.1074/jbc.272.46.29104 }}
*{{cite journal | author=Janes PW, Lackmann M, Church WB, ''et al.'' |title=Structural determinants of the interaction between the erbB2 receptor and the Src homology 2 domain of Grb7. |journal=J. Biol. Chem. |volume=272 |issue= 13 |pages= 8490-7 |year= 1997 |pmid= 9079677 |doi=  }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
*{{cite journal | author=Kishi T, Sasaki H, Akiyama N, ''et al.'' |title=Molecular cloning of human GRB-7 co-amplified with CAB1 and c-ERBB-2 in primary gastric cancer. |journal=Biochem. Biophys. Res. Commun. |volume=232 |issue= 1 |pages= 5-9 |year= 1997 |pmid= 9125150 |doi= 10.1006/bbrc.1997.6218 }}
* {{cite journal | vauthors = Fiddes RJ, Campbell DH, Janes PW, Sivertsen SP, Sasaki H, Wallasch C, Daly RJ | title = Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals a novel target selectivity for erbB3 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 13 | pages = 7717–24 | date = Mar 1998 | pmid = 9516479 | doi = 10.1074/jbc.273.13.7717 }}
*{{cite journal | author=Dong LQ, Du H, Porter SG, ''et al.'' |title=Cloning, chromosome localization, expression, and characterization of an Src homology 2 and pleckstrin homology domain-containing insulin receptor binding protein hGrb10gamma. |journal=J. Biol. Chem. |volume=272 |issue= 46 |pages= 29104-12 |year= 1997 |pmid= 9360986 |doi= }}
* {{cite journal | vauthors = Tanaka S, Mori M, Akiyoshi T, Tanaka Y, Mafune K, Wands JR, Sugimachi K | title = A novel variant of human Grb7 is associated with invasive esophageal carcinoma | journal = The Journal of Clinical Investigation | volume = 102 | issue = 4 | pages = 821–7 | date = Aug 1998 | pmid = 9710451 | pmc = 508945 | doi = 10.1172/JCI2921 }}
*{{cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi= }}
* {{cite journal | vauthors = Thömmes K, Lennartsson J, Carlberg M, Rönnstrand L | title = Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor | journal = The Biochemical Journal | volume = 341 | issue = 1 | pages = 211–6 | date = Jul 1999 | pmid = 10377264 | pmc = 1220349 | doi = 10.1042/0264-6021:3410211 }}
*{{cite journal | author=Fiddes RJ, Campbell DH, Janes PW, ''et al.'' |title=Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals a novel target selectivity for erbB3. |journal=J. Biol. Chem. |volume=273 |issue= 13 |pages= 7717-24 |year= 1998 |pmid= 9516479 |doi= }}
* {{cite journal | vauthors = Han DC, Guan JL | title = Association of focal adhesion kinase with Grb7 and its role in cell migration | journal = The Journal of Biological Chemistry | volume = 274 | issue = 34 | pages = 24425–30 | date = Aug 1999 | pmid = 10446223 | doi = 10.1074/jbc.274.34.24425 }}
*{{cite journal | author=Tanaka S, Mori M, Akiyoshi T, ''et al.'' |title=A novel variant of human Grb7 is associated with invasive esophageal carcinoma. |journal=J. Clin. Invest. |volume=102 |issue= 4 |pages= 821-7 |year= 1998 |pmid= 9710451 |doi= }}
* {{cite journal | vauthors = Jones N, Master Z, Jones J, Bouchard D, Gunji Y, Sasaki H, Daly R, Alitalo K, Dumont DJ | title = Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration | journal = The Journal of Biological Chemistry | volume = 274 | issue = 43 | pages = 30896–905 | date = Oct 1999 | pmid = 10521483 | doi = 10.1074/jbc.274.43.30896 }}
*{{cite journal | author=Thömmes K, Lennartsson J, Carlberg M, Rönnstrand L |title=Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor. |journal=Biochem. J. |volume=341 ( Pt 1) |issue= |pages= 211-6 |year= 1999 |pmid= 10377264 |doi= }}
* {{cite journal | vauthors = Vayssière B, Zalcman G, Mahé Y, Mirey G, Ligensa T, Weidner KM, Chardin P, Camonis J | title = Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho family | journal = FEBS Letters | volume = 467 | issue = 1 | pages = 91–6 | date = Feb 2000 | pmid = 10664463 | doi = 10.1016/S0014-5793(99)01530-6 }}
*{{cite journal | author=Han DC, Guan JL |title=Association of focal adhesion kinase with Grb7 and its role in cell migration. |journal=J. Biol. Chem. |volume=274 |issue= 34 |pages= 24425-30 |year= 1999 |pmid= 10446223 |doi= }}
* {{cite journal | vauthors = Kasus-Jacobi A, Béréziat V, Perdereau D, Girard J, Burnol AF | title = Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2 | journal = Oncogene | volume = 19 | issue = 16 | pages = 2052–9 | date = Apr 2000 | pmid = 10803466 | doi = 10.1038/sj.onc.1203469 }}
*{{cite journal | author=Jones N, Master Z, Jones J, ''et al.'' |title=Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration. |journal=J. Biol. Chem. |volume=274 |issue= 43 |pages= 30896-905 |year= 1999 |pmid= 10521483 |doi= }}
* {{cite journal | vauthors = Han DC, Shen TL, Guan JL | title = Role of Grb7 targeting to focal contacts and its phosphorylation by focal adhesion kinase in regulation of cell migration | journal = The Journal of Biological Chemistry | volume = 275 | issue = 37 | pages = 28911–7 | date = Sep 2000 | pmid = 10893408 | doi = 10.1074/jbc.M001997200 }}
*{{cite journal | author=Vayssière B, Zalcman G, Mahé Y, ''et al.'' |title=Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho family. |journal=FEBS Lett. |volume=467 |issue= 1 |pages= 91-6 |year= 2000 |pmid= 10664463 |doi= }}
* {{cite journal | vauthors = Lee H, Volonte D, Galbiati F, Iyengar P, Lublin DM, Bregman DB, Wilson MT, Campos-Gonzalez R, Bouzahzah B, Pestell RG, Scherer PE, Lisanti MP | title = Constitutive and growth factor-regulated phosphorylation of caveolin-1 occurs at the same site (Tyr-14) in vivo: identification of a c-Src/Cav-1/Grb7 signaling cassette | journal = Molecular Endocrinology | volume = 14 | issue = 11 | pages = 1750–75 | date = Nov 2000 | pmid = 11075810 | doi = 10.1210/me.14.11.1750 }}
*{{cite journal | author=Kasus-Jacobi A, Béréziat V, Perdereau D, ''et al.'' |title=Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2. |journal=Oncogene |volume=19 |issue= 16 |pages= 2052-9 |year= 2000 |pmid= 10803466 |doi= 10.1038/sj.onc.1203469 }}
* {{cite journal | vauthors = Skotheim RI, Abeler VM, Nesland JM, Fosså SD, Holm R, Wagner U, Flørenes VA, Aass N, Kallioniemi OP, Lothe RA | title = Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays | journal = Neoplasia | volume = 5 | issue = 5 | pages = 397–404 | year = 2003 | pmid = 14670177 | pmc = 1502610 | doi = 10.1016/s1476-5586(03)80042-8 }}
*{{cite journal | author=Han DC, Shen TL, Guan JL |title=Role of Grb7 targeting to focal contacts and its phosphorylation by focal adhesion kinase in regulation of cell migration. |journal=J. Biol. Chem. |volume=275 |issue= 37 |pages= 28911-7 |year= 2000 |pmid= 10893408 |doi= 10.1074/jbc.M001997200 }}
*{{cite journal | author=Lee H, Volonte D, Galbiati F, ''et al.'' |title=Constitutive and growth factor-regulated phosphorylation of caveolin-1 occurs at the same site (Tyr-14) in vivo: identification of a c-Src/Cav-1/Grb7 signaling cassette. |journal=Mol. Endocrinol. |volume=14 |issue= 11 |pages= 1750-75 |year= 2001 |pmid= 11075810 |doi= }}
}}
{{refend}}
{{refend}}


==External links==
== External links ==
* {{MeshName|GRB7+Adaptor+Protein}}
* {{MeshName|GRB7+Adaptor+Protein}}


{{PDB Gallery|geneid=2886}}
{{Adaptor proteins}}
{{Adaptor proteins}}


[[Category:Proteins]]
[[Category:Proteins]]
{{WikiDoc Sources}}

Latest revision as of 09:04, 31 August 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Wikidata
View/Edit Human

Growth factor receptor-bound protein 7, also known as GRB7, is a protein that in humans is encoded by the GRB7 gene.[1][2]

Function

The product of this gene belongs to a small family of adaptor proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with epidermal growth factor receptor (EGFR) and ephrin receptors. The protein plays a role in the integrin signaling pathway and cell migration by binding with focal adhesion kinase (FAK). Alternative splicing results in multiple transcript variants encoding different isoforms, although the full-length natures of only two of the variants have been determined to date.[1]

Clinical significance

GRB7 is an SH2-domain adaptor protein that binds to receptor tyrosine kinases and provides the intra-cellular direct link to the Ras proto-oncogene. Human GRB7 is located on the long arm of chromosome 17, next to the ERBB2 (alias HER2/neu) proto-oncogene.

These two genes are commonly co-amplified (present in excess copies) in breast cancers. GRB7 thought to be involved in migration[citation needed], is well known to be over-expressed in testicular germ cell tumors, esophageal cancers, and gastric cancers.

Interactions

GRB7 has been shown to interact with:

Model organisms

Model organisms have been used in the study of GRB7 function. A conditional knockout mouse line called Grb7tm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[8] Male and female animals underwent a standardized phenotypic screen[9] to determine the effects of deletion.[10][11][12][13] Additional screens performed: - In-depth immunological phenotyping[14]

References

  1. ↑ 1.0 1.1 "Entrez Gene: GRB7 growth factor receptor-bound protein 7".
  2. ↑ Tanaka S, Mori M, Akiyoshi T, Tanaka Y, Mafune K, Wands JR, Sugimachi K (Aug 1998). "A novel variant of human Grb7 is associated with invasive esophageal carcinoma". The Journal of Clinical Investigation. 102 (4): 821–7. doi:10.1172/JCI2921. PMC 508945. PMID 9710451.
  3. ↑ Han DC, Shen TL, Miao H, Wang B, Guan JL (Nov 2002). "EphB1 associates with Grb7 and regulates cell migration". The Journal of Biological Chemistry. 277 (47): 45655–61. doi:10.1074/jbc.M203165200. PMID 12223469.
  4. ↑ Kasus-Jacobi A, Béréziat V, Perdereau D, Girard J, Burnol AF (Apr 2000). "Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2". Oncogene. 19 (16): 2052–9. doi:10.1038/sj.onc.1203469. PMID 10803466.
  5. ↑ Han DC, Guan JL (Aug 1999). "Association of focal adhesion kinase with Grb7 and its role in cell migration". The Journal of Biological Chemistry. 274 (34): 24425–30. doi:10.1074/jbc.274.34.24425. PMID 10446223.
  6. ↑ Pandey A, Liu X, Dixon JE, Di Fiore PP, Dixit VM (May 1996). "Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7". The Journal of Biological Chemistry. 271 (18): 10607–10. doi:10.1074/jbc.271.18.10607. PMID 8631863.
  7. ↑ Vayssière B, Zalcman G, Mahé Y, Mirey G, Ligensa T, Weidner KM, Chardin P, Camonis J (Feb 2000). "Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho family". FEBS Letters. 467 (1): 91–6. doi:10.1016/s0014-5793(99)01530-6. PMID 10664463.
  8. ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  9. ↑ 9.0 9.1 "International Mouse Phenotyping Consortium".
  10. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  11. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  12. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  13. ↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  14. ↑ 14.0 14.1 "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

External links

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