c-Src signaling induced by the adapters Sin and Cas is mediated by Rap1 GTPase
Molecular and Cellular Biology 20(19), 7363- 7377, October 2000
Luzhou Xing, Ph.D
Department of Biological Sciences
C. Ge, R. Zeltser, G. Maskevitch, B.J. Mayer & K. Alexandropoulos
Oncogenic Src proteins have been extensively studied to gain insight into the signaling mechanisms of Src. To better understand signaling through wild-type Src, we used an approach that involves activation of Src signaling through the binding of physiologic ligands to the Src SH3 domain. To this end, we used full-length and truncated versions of the multiadapter molecules Cas and Sin to activate c-Src, and we examined the intracellular pathways that mediate Src signaling under these conditions. We show that although all proteins bind to and are phosphorylated by c-Src, quantitative differences exist in the ability of the different ligands to activate c-Src signaling. In addition, we show that Sin- and Cas-induced Src signaling, as assayed by transcriptional activation, is exclusively mediated through a pathway that involves the adapter Crk and the GTP-binding protein Rap1. These data are in contrast to previous observations showing Ras to mediate signaling downstream of transforming Src alleles.