Purification notesab61795 was affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific phosphopeptide. The antibody against non-phosphopeptide was removed by chromatography using non-phosphopeptide corresponding to the phosphorylation site.
The application notes include recommended starting dilutions; optimal dilutions/concentrations should be determined by the end user.
1/500 - 1/1000. Detects a band of approximately 67 kDa (predicted molecular weight: 67 kDa).
FunctionAdapter 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.
Tissue specificityWidely expressed in fetal and adult tissues, including fetal and postnatal liver, lung, kidney, skeletal muscle, heart, spleen, skin and brain.
Sequence similaritiesBelongs to the GRB7/10/14 family. Contains 1 PH domain. Contains 1 Ras-associating domain. Contains 1 SH2 domain.
DomainThe PH domain binds relatively non-specifically to several phosphoinositides, including PI(5)P, PI(4,5)P2, PI(3,4)P2 and PI(3,4,5)P3, with modest affinities.
Post-translational modificationsphosphorylated on serine residues upon EGF, FGF and PDGF stimulation.
Cellular localizationCytoplasm. 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.