Grb2

Grb2 is an adaptor protein involved in signal transduction/cell communication. The name Grb2 is an abbreviation of Growth factor receptor-bound protein 2.

PBB_Summary
section_title =
summary_text = The protein encoded by this gene binds the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the Sem5 gene of "Caenorhabditis elegans", which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [cite web | title = Entrez Gene: GRB2 growth factor receptor-bound protein 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2885| accessdate = ]

Function and expression

Grb2 is widely expressed and is essential for multiple cellular functions. Inhibition of Grb2 function impairs developmental processes in various organisms and blocks transformation and proliferation of various cell types, and so it is not surprising that a targeted gene disruption of Grb2 in mouse is lethal at an early embryonic stage. Grb2 is best known for its ability to link the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases, ERK1,2. Grb2 is composed of an SH2 domain flanked on each side by an SH3 domain. Grb2 has two closely related proteins with similar domain organizations, Gads and Grap. Gads and Grap are expressed specifically in hematopoietic cells and function in the coordination of tyrosine kinase mediated signal transduction.

Domains

The SH2 domain of Grb2 binds to phosphorylated tyrosine containing peptides on receptors or scaffold proteins with a preference for pY-X-N-X, where X is generally a hydrophobic residue such as valine (see [http://sh2.uchicago.edu/sh2/cgi-bin/prot_page.cgi?gene=GRB2 The SH2 Website] ).

The N-terminal SH3 domain binds to proline-rich peptide peptides and can bind to the Ras-guanine exchange factor SOS.

The C-terminal SH3 domain binds to peptides conforming to a P-X-I/L/V/-D/N-R-X-X-K-P motif that allows it to specifically bind to proteins such as Gab-1. [cite journal |author=Berry DM, Nash P, Liu SK, Pawson T, McGlade CJ |title=A high-affinity Arg-X-X-Lys SH3 binding motif confers specificity for the interaction between Gads and SLP-76 in T cell signaling |journal=Curr. Biol. |volume=12 |issue=15 |pages=1336–41 |year=2002 |pmid=12176364 |doi=]

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Colledge M, Froehner SC |title=Interaction between the nicotinic acetylcholine receptor and Grb2. Implications for signaling at the neuromuscular junction. |journal=Ann. N. Y. Acad. Sci. |volume=841 |issue= |pages= 17–27 |year= 1998 |pmid= 9668219 |doi=
*cite journal | author=Ramesh N, Antón IM, Martínez-Quiles N, Geha RS |title=Waltzing with WASP. |journal=Trends Cell Biol. |volume=9 |issue= 1 |pages= 15–9 |year= 1999 |pmid= 10087612 |doi=
*cite journal | author=O'Sullivan E, Kinnon C, Brickell P |title=Wiskott-Aldrich syndrome protein, WASP. |journal=Int. J. Biochem. Cell Biol. |volume=31 |issue= 3-4 |pages= 383–7 |year= 1999 |pmid= 10224664 |doi=
*cite journal | author=Schlaepfer DD, Hauck CR, Sieg DJ |title=Signaling through focal adhesion kinase. |journal=Prog. Biophys. Mol. Biol. |volume=71 |issue= 3-4 |pages= 435–78 |year= 1999 |pmid= 10354709 |doi=
*cite journal | author=Vidal M, Liu WQ, Gril B, "et al." |title= [Design of new anti-tumor agents interrupting deregulated signaling pathways induced by tyrosine kinase proteins. Inhibition of protein-protein interaction involving Grb2] |journal=J. Soc. Biol. |volume=198 |issue= 2 |pages= 133–7 |year= 2004 |pmid= 15368963 |doi=

External links

* [http://sh2.uchicago.edu/sh2/cgi-bin/prot_page.cgi?gene=GRB2 The Grb2 protein page on The SH2 Website]
* [http://www.genecards.org/cgi-bin/carddisp.pl?gene=GRB2&search=grb2 GeneCards entry for Grb2]
* [http://www.hprd.org/protein/00150 Human Protein Resource Database entry for Grb2]
* [http://www.ihop-net.org/UniPub/iHOP/gs/88808.html Grb2 information on iHOP (Information Hyperlinked over Proteins)]

External links

*

ee also

*MAPK/ERK pathway

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