Tumor promoters cause changes in the state of phosphorylation and apparent molecular weight of a tyrosine protein kinase in T lymphocytes.
The T cell lymphoma LSTRA contains an elevated level of a tyrosine protein kinase of molecular weight of 56,000 (pp56Tcell) that is present in normal T lymphocytes. Treatment of 32P-labeled LSTRA cells with the phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), followed by immunoprecipitation of pp56Tcell, revealed that PMA causes complex changes in the state of phosphorylation of pp56Tcell, and the appearance of several new forms of pp56Tcell with higher apparent molecular weights on sodium dodecyl sulfate-polyacrylamide gels. The 32P-labeled pp56Tcell from untreated LSTRA cells contains phosphotyrosine and phosphoserine in a ratio of 2:1. After treatment of LSTRA cells with PMA, the form of pp56Tcell that runs with a molecular weight of 56,000 has approximately equal amounts of phosphotyrosine and phosphoserine, while the higher molecular weight forms of pp56Tcell seen after PMA have 3-4 times more phosphoserine than phosphotyrosine. The induction by PMA of higher molecular weight forms of pp56Tcell could also be demonstrated in preparations of normal human T lymphocytes. The changes in the state of phosphorylation of pp56Tcell after treatment of cells with PMA are consistent with the possibility that pp56Tcell is an in vivo substrate for protein kinase C and provide documentation for a linkage between a mitogenic agent and pp56Tcell.
Casnellie
J E
JE
Lamberts
R J
RJ
D000818:Animals; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007158:Immunologic Techniques; D007163:Immunosorbent Techniques; D008223:Lymphoma / Q000201:enzymology; D051379:Mice; D008970:Molecular Weight; D010704:Phorbols / Q000494:pharmacology*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D019000:Phosphotyrosine; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D010704:Phorbols; D010768:Phosphoserine; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate