Regulation of Laloo by the Xenopus C-terminal Src kinase (Xcsk) during early vertebrate development

Mesoderm formation in the frog, Xenopus laevis, is dependent on the activit y of one or more members of the Src family kinases; the molecular interacti ons underlying this requirement are not well understood. The C-terminal Src Kinase (Csk) is a potent inhibitor of Src activity, and is required for no rmal mammalian development; here we report the characterization of Xenopus Csk (Xcsk). Xcsk is widely expressed during early development, physically i nteracts with the Src kinase Laloo, and inhibits the generation of mesoderm by the Src kinases. Xcsk activity requires a functional kinase domain; fur thermore, a kinase-inactive Xcsk mutant potently synergizes with Laloo duri ng early vertebrate development, suggesting a fundamental role for the Src kinase-Csk regulatory circuit during mesoderm induction, in vivo.