GRB10
Description
The GRB10 (growth factor receptor bound protein 10) is a protein-coding gene located on chromosome 7.
Growth factor receptor-bound protein 10, also known as insulin receptor-binding protein Grb-IR, is a protein that in humans is encoded by the GRB10 gene. 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 insulin receptors and insulin-like growth-factor receptors (e.g., IGF1R and IGF2R). Overexpression of some isoforms of the encoded protein inhibits tyrosine kinase activity and results in growth suppression. This gene is imprinted in a highly isoform- and tissue-specific manner. Alternatively spliced transcript variants encoding different isoforms have been identified. Mice whose paternally inherited Grb10 gene is inactivated are more aggressive while those whose maternally inherited allele is inactivated exhibit foetal overgrowth and are significantly bigger than wild-type litter-mates. GRB10 has been shown to interact with Abl gene, BCR gene, C-Raf, c-Kit, Insulin receptor, Insulin-like growth factor 1 receptor, MAP2K1, and RET proto-oncogene.
GRB10 is an adapter protein that regulates the coupling of cell surface receptor kinases with specific signaling pathways. It binds to and inhibits signals from activated receptor tyrosine kinases, including the insulin (INSR) and insulin-like growth factor (IGF1R) receptors. This inhibitory effect is achieved by two mechanisms: interference with the signaling pathway and increased receptor degradation. GRB10 delays and reduces AKT1 phosphorylation in response to insulin stimulation, blocks the association between INSR and IRS1/IRS2, and prevents insulin-stimulated IRS1/IRS2 tyrosine phosphorylation. It recruits NEDD4 to IGF1R, leading to IGF1R ubiquitination, increased internalization, and degradation by both the proteasomal and lysosomal pathways. GRB10 may also mediate insulin-stimulated ubiquitination of INSR, leading to proteasomal degradation. Additionally, it negatively regulates Wnt signaling by interacting with the intracellular portion of LRP6 and interfering with the binding of AXIN1 to LRP6. GRB10 is a positive regulator of the KDR/VEGFR-2 signaling pathway and may inhibit NEDD4-mediated degradation of KDR/VEGFR-2.
GRB10 is also known as GRB-IR, Grb-10, IRBP, MEG1, RSS.
