Cellular depletion of p56lck during thymocyte apoptosis.
The src-related protein tyrosine kinase p56lck is thought to be important in regulating maturation and functional responsiveness of T cells and thymocytes. In the present studies we report that expression of p56lck is suppressed during apoptosis. Using primary cultures of rat thymocytes, we found that agents that are effective in inducing apoptosis, including okadaic acid, dexamethasone, and antibodies to the CD3 receptor, also deplete cells of p56lck. This process is rapid, occurring within 24 h, and is not due to cytotoxicity. Inhibition of DNA fragmentation in apoptotic cells with the endonuclease inhibitor ZnCl2 failed to prevent depletion of p56lck, suggesting that it was not a consequence of the DNA degradation process. Using the thymic lymphoma cell line LSTRA, apoptosis was also associated with cellular depletion of p56lck. In contrast to thymocytes, this process required 48-72 h possibly because these cells overexpress p56lck. Although at this time we are uncertain as to the precise role of p56lck in the process of apoptosis, our results indicate that changes in the expression of this protein in thymocytes is an important marker of programmed cell death.
Garcia-Welsh
A
A
Department of Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway 08854.
Laskin
D L
DL
Shuler
R L
RL
Laskin
J D
JD
D000818:Animals; D017209:Apoptosis; D002712:Chlorides / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019319:Okadaic Acid; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D017967:Zinc Compounds / Q000494:pharmacology
D002712:Chlorides; D004988:Ethers, Cyclic; D017967:Zinc Compounds; D019319:Okadaic Acid; D003907:Dexamethasone; C016837:zinc chloride; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)