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 membrane-targeted form of Csk (Src/Csk) and its kinase-defective variant (DK-Src/Csk) were expressed in the embryonic carcinoma cell line P19. Expression of Src/Csk, but not DK-Src/Csk, caused reduction of the specific activities of Src and Fyn in the differentiated P19 cells. During neural differentiation, the specific activity of Src was elevated in the control P19 cells, whereas the activation was completely eliminated in the Src/Csk transfectant. In normally differentiated P19 cells, cross-linking of a cell adhesion molecule, L1, induced a short-term activation of Src and Fyn. In the Src/Csk transfectant, L1 stimulation induced delayed activation of Src and Fyn peaking at much lower levels than in the control cells. Src/Csk transfectants developed normally in the initial stages of neural differentiation, but exhibited an apparent defect in cell-to-cell interaction, i.e. neurite fasciculation and aggregation of cell bodies, in the latter stages. These findings imply that Csk is involved in the regulation of Src family kinases that play roles in cell-to-cell interaction mediated by cell adhesion molecules.
Takayama
Y
Y
Division of Protein Metabolism, Institute for Protein Research, Osaka University, Suita, Japan.
Nada
S
S
Nagai
K
K
Okada
M
M
D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D018236:Carcinoma, Embryonal / Q000473:pathology*; D002454:Cell Differentiation; D039841:Leukocyte L1 Antigen Complex; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases
D039841:Leukocyte L1 Antigen Complex; D019006:Neural Cell Adhesion Molecules; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases