GRB2

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

The protein encoded by this gene binds receptors such as the is_associated_with::epidermal growth factor receptor and contains one is_associated_with::SH2 domain and two is_associated_with::SH3 domains. Its two SH3 domains direct complex formation with is_associated_with::proline-rich regions of other proteins, and its SH2 domain binds is_associated_with::tyrosine phosphorylated sequences. This gene is similar to the sem-5 gene of is_associated_with::Caenorhabditis elegans, which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene.

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 is_associated_with::embryonic stage. Grb2 is best known for its ability to link the is_associated_with::epidermal growth factor receptor is_associated_with::tyrosine kinase to the activation of Ras and its downstream kinases, ERK1,2. Grb2 is composed of an is_associated_with::SH2 domain flanked on each side by an is_associated_with::SH3 domain. Grb2 has two closely related proteins with similar domain organizations, Gads and Grap. Gads and Grap are expressed specifically in is_associated_with::hematopoietic cells and function in the coordination of is_associated_with::tyrosine kinase mediated is_associated_with::signal transduction.

Domains
The is_associated_with::SH2 domain of Grb2 binds to is_associated_with::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 ).

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

The C-terminal is_associated_with::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.

Interactions
Grb2 has been shown to interact with:


 * is_associated_with::ADAM15,
 * is_associated_with::Abl gene,
 * is_associated_with::Arachidonate 5-lipoxygenase,
 * is_associated_with::B-cell linker,
 * is_associated_with::BCAR1,
 * is_associated_with::BCR gene,
 * is_associated_with::Beta-2 adrenergic receptor,
 * is_associated_with::C-Met,
 * CBLB,
 * is_associated_with::CD117,
 * is_associated_with::CD22,
 * is_associated_with::CD28,
 * is_associated_with::CDKN1B,
 * CRK,
 * is_associated_with::Cbl gene,
 * is_associated_with::Colony stimulating factor 1 receptor,
 * is_associated_with::DCTN1,
 * is_associated_with::DNM1,
 * is_associated_with::Dock180,
 * is_associated_with::Dystroglycan,
 * is_associated_with::EPH receptor A2,
 * is_associated_with::ETV6,
 * is_associated_with::Epidermal growth factor receptor,
 * is_associated_with::Erythropoietin receptor,
 * is_associated_with::FRS2,
 * is_associated_with::Fas ligand,
 * is_associated_with::GAB1,
 * is_associated_with::GAB2,
 * is_associated_with::Glycoprotein 130,
 * is_associated_with::Granulocyte colony-stimulating factor receptor,
 * is_associated_with::HER2/neu,
 * is_associated_with::HNRNPC,
 * is_associated_with::Huntingtin,
 * is_associated_with::INPP5D,
 * is_associated_with::IRS1,
 * ITK,
 * is_associated_with::Janus kinase 1,
 * is_associated_with::Janus kinase 2,
 * is_associated_with::KHDRBS1,
 * is_associated_with::Linker of activated T cells,
 * is_associated_with::Lymphocyte cytosolic protein 2,
 * is_associated_with::MAP2,
 * is_associated_with::MAP3K1
 * is_associated_with::MAP4K1,
 * is_associated_with::MED28,
 * is_associated_with::MST1R,
 * is_associated_with::MUC1,
 * is_associated_with::Mitogen-activated protein kinase 9,
 * is_associated_with::NCKIPSD,
 * is_associated_with::NEU3,
 * is_associated_with::PDGFRB,
 * is_associated_with::PIK3R1,
 * is_associated_with::PLCG1,
 * is_associated_with::PRKAR1A,
 * is_associated_with::PTK2,
 * is_associated_with::PTPN11,
 * is_associated_with::PTPN12,
 * is_associated_with::PTPN1,
 * is_associated_with::PTPN6,
 * is_associated_with::PTPRA,
 * is_associated_with::RAPGEF1,
 * is_associated_with::RET proto-oncogene,
 * is_associated_with::SH2B1,
 * is_associated_with::SH3KBP1,
 * is_associated_with::SHC1,
 * is_associated_with::SOS1,
 * Src,
 * is_associated_with::Syk,
 * is_associated_with::TNK2,
 * is_associated_with::TrkA,
 * is_associated_with::VAV1,
 * is_associated_with::VAV2,
 * is_associated_with::VAV3, and
 * is_associated_with::Wiskott-Aldrich syndrome protein.