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Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene.[1][2]

The protein encoded by this gene binds receptors such as 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 sem-5 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.[3]

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. It is thus not surprising that targeted gene disruption of Grb2 in mice 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.


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 [2]).

The N-terminal SH3 domain binds to proline-rich 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.[4]


Grb2 has been shown to interact with:

See also


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Further reading

  • Colledge M, Froehner SC (May 1998). "Interaction between the nicotinic acetylcholine receptor and Grb2. Implications for signaling at the neuromuscular junction". Annals of the New York Academy of Sciences. 841: 17–27. doi:10.1111/j.1749-6632.1998.tb10907.x. PMID 9668219.
  • Ramesh N, Antón IM, Martínez-Quiles N, Geha RS (Jan 1999). "Waltzing with WASP". Trends in Cell Biology. 9 (1): 15–9. doi:10.1016/S0962-8924(98)01411-1. PMID 10087612.
  • O'Sullivan E, Kinnon C, Brickell P (1999). "Wiskott-Aldrich syndrome protein, WASP". The International Journal of Biochemistry & Cell Biology. 31 (3–4): 383–7. doi:10.1016/S1357-2725(98)00118-6. PMID 10224664.
  • Schlaepfer DD, Hauck CR, Sieg DJ (1999). "Signaling through focal adhesion kinase". Progress in Biophysics and Molecular Biology. 71 (3–4): 435–78. doi:10.1016/S0079-6107(98)00052-2. PMID 10354709.
  • Vidal M, Liu WQ, Gril B, Assayag F, Poupon MF, Garbay C (2004). "[Design of new anti-tumor agents interrupting deregulated signaling pathways induced by tyrosine kinase proteins. Inhibition of protein-protein interaction involving Grb2]". Journal De La Société De Biologie. 198 (2): 133–7. PMID 15368963.

External links