Growth Factor Receptor-Bound Protein 2 (GRB2) is a crucial adaptor protein involved in signal transduction and cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene. This protein plays a pivotal role in various cellular processes, including cell growth, differentiation, and survival.
GRB2 is composed of one SH2 (Src Homology 2) domain flanked by two SH3 (Src Homology 3) domains . The SH2 domain binds to phosphorylated tyrosine residues on receptor tyrosine kinases (RTKs) or other scaffold proteins, while the SH3 domains interact with proline-rich regions of other proteins .
GRB2 is essential for linking RTKs to the Ras signaling pathway. Upon ligand binding and activation of RTKs, GRB2 is recruited to the phosphorylated tyrosine residues on the receptor through its SH2 domain. GRB2 then binds to the SOS protein via its SH3 domains, facilitating the activation of Ras, a small GTPase . This activation triggers a cascade of downstream signaling events, ultimately leading to cell proliferation, survival, and differentiation .
GRB2 is widely expressed and is vital for multiple cellular functions. Inhibition of GRB2 function impairs developmental processes in various organisms and blocks the transformation and proliferation of various cell types . Targeted gene disruption of GRB2 in mice is lethal at an early embryonic stage, highlighting its critical role in development .
GRB2’s involvement in key signaling pathways makes it a potential target for therapeutic interventions. Abnormalities in GRB2 function or expression are associated with various diseases, including cancers and immune disorders . Understanding the structure and function of GRB2 can provide novel insights and strategies for developing therapeutic approaches aimed at modulating its activity .