Figure 2.

Roles of Crk proteins in oncogenic signaling. (A) Downstream of growth factor or integrin stimulation, Crk adaptors act in signal transduction by binding to phosphorylated tyrosine motifs (e.g., Gab1 or p130Cas)^99,100 and acting as a bridge to SH3 binding partners (e.g., C3G, Dock180).^3,48 (B) Crk proteins enhance the signaling of cellular tyrosine kinases possibly through direct interactions enhancing an active conformation (e.g., Abl)³³ or indirectly through the removal of negative regulation or substrate selection (e.g., Src).^52,53 (C) Crk proteins engage upstream of oncogenic signaling through regulating enhanced Met recycling and activation of integrin signaling cascades.^57,60