GRB10

The product of this gene belongs to a small family of adapter 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. 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. [provided by RefSeq]

Full Name

growth factor receptor-bound protein 10

Function

Adapter protein which modulates coupling of a number of cell surface receptor kinases with specific signaling pathways. Binds to, and suppress signals from, activated receptors tyrosine kinases, including the insulin (INSR) and insulin-like growth factor (IGF1R) receptors. The inhibitory effect can be achieved by 2 mechanisms: interference with the signaling pathway and increased receptor degradation. Delays and reduces AKT1 phosphorylation in response to insulin stimulation. Blocks association between INSR and IRS1 and IRS2 and prevents insulin-stimulated IRS1 and IRS2 tyrosine phosphorylation. Recruits NEDD4 to IGF1R, leading to IGF1R ubiquitination, increased internalization and degradation by both the proteasomal and lysosomal pathways. May play a role in mediating insulin-stimulated ubiquitination of INSR, leading to proteasomal degradation. Negatively regulates Wnt signaling by interacting with LRP6 intracellular portion and interfering with the binding of AXIN1 to LRP6. Positive regulator of the KDR/VEGFR-2 signaling pathway. May inhibit NEDD4-mediated degradation of KDR/VEGFR-2.

Biological Process

ERK1 and ERK2 cascade Source: Ensembl
Gene expression Source: Ensembl
Insulin-like growth factor receptor signaling pathway Source: Ensembl
Insulin receptor signaling pathway Source: BHF-UCL
Negative regulation of glucose import Source: BHF-UCL
Negative regulation of glycogen biosynthetic process Source: BHF-UCL
Negative regulation of insulin receptor signaling pathway Source: BHF-UCL
Negative regulation of phosphorylation Source: Ensembl
Negative regulation of Wnt signaling pathway Source: UniProtKB
Positive regulation of cold-induced thermogenesis Source: YuBioLab
Positive regulation of phosphorylation Source: BHF-UCL
Positive regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
Response to insulin Source: BHF-UCL
Vascular associated smooth muscle cell migration Source: Ensembl

Cellular Location

Cytoplasm. When complexed with NEDD4 and IGF1R, follows IGF1R internalization, remaining associated with early endosomes. Uncouples from IGF1R-containing endosomes before the sorting of the receptor to the lysosomal compartment (By similarity).

PTM

Phosphorylated on serine residues upon EGF, FGF and PDGF stimulation (By similarity). Phosphorylated at Tyr-67 by TEC.