Stem cell factor induces phosphatidylinositol 3 '-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells

Stem cell factor (SCF) has an important role in the proliferation, differen tiation, survival, end migration of hematopoietic cells. SCF exerts its eff ects by binding to cKit, a receptor with intrinsic tyrosine kinase activity . Activation of phosphatidylinositol 3'-kinase (PI3-K) by cKit was previous ly shown to contribute to many SCF-induced cellular responses. Therefore, P I3-K-dependentsignaling pathways activated by SCF were investigated. The PI 3K-dependent:activation and phosphorylation of the tyrosine kinase Tec and the adapter molecule p62Dok-1 are reported. The study shows that Tec and Do k-1 form a stable complex with Lyn and 2 unidentified phosphoproteins of 56 and 140 kd, Both the Tec homology and the SH2 domain of Tec were identifie d as being required for the interaction with Dok-1, whereas 2 domains in Do k-1 appeared to mediate the association with Tee. In addition, Tec and Lyn were shown to phosphorylate Dok-1, whereas phosphorylated Dok-1 was demonst rated to bind to the SH2 domains of several signaling molecules activated b y SCF, including Abl, CrkL, SHIP, and PLC gamma -1, but not those of Vav an d Shc. These findings suggest that p62Dok-1 may function as an important sc affold molecule in cKit-mediated signaling. (C) 2000 by The American Societ y of Hematology.