Distinctive functions of Syk and Lyn in mediating osmotic stress- and ultraviolet C irradiation-induced apoptosis in chicken B cells.
By taking advantage of the established chicken B cell line, DT40 cells, which do not express tyrosine kinase Syk or Lyn, functional roles of Syk and Lyn in apoptotic response elicited by cellular stress were investigated. DT40 cells underwent apoptosis after hyperosmotic stress. In Syk-deficient DT40 cells, this apoptotic process was significantly enhanced. Ectopic expression of wild type, but not kinase-inactive, porcine Syk in Syk-deficient cells rescued cells from osmotic stress-induced apoptosis, demonstrating that the presence of functionally active Syk is necessary to protect cells from osmotic stress-induced apoptosis. In comparison, there was no effect on osmotic stress-induced apoptosis in Lyn-deficient DT40 cells. Interestingly, while Syk was not involved in ultraviolet C (UVC)-induced apoptosis, a deficiency of Lyn rendered cells resistant to UVC irradiation. These observations defined Syk and Lyn as important mediators of apoptosis in DT40 cells in response to osmotic stress and UVC irradiation, respectively. Furthermore, osmotic stress, but not UVC irradiation, could activate c-Jun N-terminal kinase (JNK) in DT40 cells. A deficiency in either Syk or Lyn did not affect the osmotic stress-induced activation of JNK. We, therefore, concluded that Syk and Lyn regulate the apoptotic responses to osmotic stress and UVC irradiation independently of the JNK pathway in DT40 cells.
Qin
S
S
Departments of Biochemistry, Kobe University School of Medicine, Kobe 650, Japan.
Minami
Y
Y
Kurosaki
T
T
Yamamura
H
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D053938:DNA Fragmentation; D004307:Dose-Response Relationship, Radiation; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D009994:Osmolar Concentration; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011836:Radiation Tolerance; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology / Q000528:radiation effects; D013312:Stress, Physiological; D013552:Swine; D000072377:Syk Kinase; D014162:Transfection; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D019061:src-Family Kinases / Q000378:metabolism*
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D019061:src-Family Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases