ShcA, an SH2-containing adapter protein, acts as a scaffold for the assembly of signaling proteins involved in the activation of the Ras-MAPK pathway, and potentially other signaling pathways. ShcA is one of the binding partners of endogenous Tie2 receptor on vascular endothelial cells. After Tie2 stimulation by Ang-1 interaction, ShcA associates with Tie2 and becomes tyrosine-phosphorylated. ShcA interacts with the cytoplasmic domain of Tie2 and Y1102 of Tie2 was identified as the primary binding site for the SH2 domain of ShcA. ShcA leads to a reduction of tyrosine phosphorylation of p85 subunit of PI3-kinase and is involved in the inhibition of endothelial cell migration and survival.
Bussolino, F, Napione, L, Cascone, I, Lanfrancone, L, Maniero, F, Audero, E, Arese, M
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