REGULATION OF SRC FAMILY KINASES IN THE DEVELOPING RAT-BRAIN - CORRELATION WITH THEIR REGULATOR KINASE, CSK

We have so far suggested that the functions of Src family protein-tyro sine kinases are under the control of their regulator kinase, Csk. To evaluate the role of Csk-mediated regulation in neural tissues, we exa mined the correlation between the activities of Src family kinases and the expression level of Csk during development of the rat brain. Csk was expressed at high levels in the developing embryonic brain and the n rapidly decreased as the brain matured. Consistent with the decrease in the Csk level, the kinase activity of a member of the Src family, Fyn, was greatly enhanced, but that of Src was not correlated inversel y with the level of Csk expression. Src exhibited elevated activity in the developing brain, in which a neuronal form of Src (N-Src) is expr essed as the dominant form of Src. Although N-Src was readily down-reg ulated by Csk when coexpressed in yeast, it showed much higher specifi c activity than c-Src, even in the repressed form. These findings sugg est that neural tissues acquire high activities of Src family kinases, which might be important for differentiation and development of the n ervous system, through induction of the active form of Src (N-Src) and down-regulation of their suppresser, Csk.