ABL kinase‐dependent phosphorylation of SH proteins promotes their direct interaction with CRK family

CT10 regulator of kinase (CRK) and CRK‐Like (CRKL) are important Src homology 2 (SH2)‐ and SH3‐domain containing signaling adaptors, which drive cell adhesion, motility, differentiation, and proliferation. Their genetically defined and overlapping roles include facilitating proper development of the vertebrate central nervous system. All four members of the SH2‐domain containing (SH) protein family are enriched in YXXP motifs, which when the initial tyrosine is phosphorylated form the preferred binding motif of CRK family SH2 domains. We show that ABL kinase drives tyrosine phosphorylation of SH protein YXXP motifs and induces their direct binding to the SH2 domains of CRK family adaptors. The implications of the interactions between CRK/CRKL and SH proteins include signal attenuation and relocation of CRK adaptor signaling.