GRB10 Antibody – Rabbit Polyclonal

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, with expression observed from the paternal allele in the brain, and from the maternal allele in the placental trophoblasts. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010]

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. Ref.17 Ref.19 Ref.21 Ref.22

Enzyme regulation: Phosphorylation by mTORC1 stabilizes and activates GRB10 constituting a feedback pathway by which mTORC1 inhibits INSR-dependent signaling. Ref.28

Subunit structure: Interacts with ligand-activated tyrosine kinase receptors, including FGFR1, INSR, IGF1R, MET and PDGFRB in a phosphotyrosine-dependent manner through the SH2 domain

By similarity. Poorly binds to the EGFR

By similarity. Directly interacts with MAP3K14/NIK and is recruited to the EGFR-ERBB2 complex. Interacts with GIGYF1/PERQ1 and GIGYF2/TNRC15

By similarity. When unphosphorylated, interacts with AKT1 and when phosphorylated with YWHAE/14-3-3 epsilon. Interacts with NEDD4. Interacts with LRP6, thus interfering with the binding of AXIN1 to LRP6

By similarity. Binds to activated NRAS. Ref.17 Ref.18 Ref.19 Ref.20 Ref.30

Subcellular location: Cytoplasm

By similarity. Note: 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.

Tissue specificity: Widely expressed in fetal and adult tissues, including fetal and postnatal liver, lung, kidney, skeletal muscle, heart, spleen, skin and brain. Ref.16

Domain: The PH domain binds relatively non-specifically to several phosphoinositides, including PI5P, PI(4,5)P2, PI(3,4)P2 and PI(3,4,5)P3, with modest affinities.

Post-translational modification: Phosphorylated on serine residues upon EGF, FGF and PDGF stimulation

By similarity. Phosphorylated at Tyr-67 by TEC. Ref.6 Ref.15 Ref.20 Ref.28

Miscellaneous: The GRB10 locus is imprinted. During embryonic development, the expression in the brain and spinal cord is from the paternal allele, while in placental villous trophoblasts and skeletal muscle, it is from the maternal one. Expression is biallelic in most other tissues. Paternal expression in the brain is maintained throughout adulthood. Imprinting often is isoform-specific.GRB10 is unlikely to be responsible for Silver-Russell syndrome (SRS).

Sequence similarities: Belongs to the GRB7/10/14 family.Contains 1 PH domain.Contains 1 Ras-associating domain.Contains 1 SH2 domain.

Sequence caution: The sequence BAA13198.2 differs from that shown. Reason: Erroneous initiation.