ROLE OF CSK IN NEURAL DIFFERENTIATION OF THE EMBRYONIC CARCINOMA CELL-LINE P19

To examine the neural function of Csk (C-terminal Src kinase), a membr ane-targeted form of Csk (Src/Csk) and its kinase-defective variant (D K-Src/Csk) were expressed in the embryonic carcinoma cell line P19. Ex pression of Src/Csk, but not DK-Src/Csk, caused reduction of the speci fic activities of Src and Fyn in the differentiated P19 cells. During neural differentiation, the specific activity of Src was elevated in t he control P19 cells, whereas the activation was completely eliminated in the Src/Csk transfectant. In normally differentiated P19 cells, cr oss-linking of a cell adhesion molecule, L1, induced a short-term acti vation of Src and Fyn. In the Src/Csk transfectant, L1 stimulation ind uced delayed activation of Src and Fyn peaking at much lower levels th an in the control cells. Src/Csk transfectants developed normally in t he initial stages of neural differentiation, but exhibited an apparent defect in cell-to-cell interaction, i.e. neurite fasciculation and ag gregation of cell bodies, in the latter stages. These findings imply t hat Csk is involved in the regulation of Src family kinases that play roles in cell-to-cell interaction mediated by cell adhesion molecules. (C) 1997 Federation of European Biochemical Societies.