Altered expression of protein kinase C, lck, and CD45 in a 12-O-tetradecanoylphorbol-13-acetate-dependent leukemic T-cell variant that expresses a high level of interleukin-2 receptor.
The compound 12-O-tetradecanoylphorbol-13-acetate (TPA) is extremely toxic to the P13 subclone of the Jurkat human T-cell leukemia line. By selecting for growth in the presence of TPA, we have isolated two TPA-resistant variants of these cells, P13-50 and P13-5/A8. Studies of protein kinase C (PKC) enzyme activity, immunoblot analyses, and assays for PKC mRNAs indicate that both of these variants express lower levels of PKC than do the parental P13 cells. We suggest that this protects them from the toxic effects of TPA. The P13-5/A8 cells are of particular interest because not only are they resistant to TPA toxicity but they actually require TPA for optimal growth. These cells have a more profound decrease in PKC expression that do P13-50 cells. In addition, P13-5/A8 cells display very little, if any, surface expression of CD45, a receptor-linked tyrosine protein phosphatase, and lck, a lymphocyte-specific tyrosine kinase. On the other hand, they express a very high level of interleukin-2 receptor. A model is proposed that suggests that these cells are dependent on TPA because they have defects in both the PKC and tyrosine kinase signal transduction pathways, and that TPA compensates for these defects by providing a strong stimulus to the residual level of PKC. This variant may be useful for studying the interactions between tyrosine kinase and PKC pathways in controlling the various functions of T lymphocytes.
Tchou-Wong
K M
KM
Comprehensive Cancer Center, Columbia University, New York, New York 10032.
Weinstein
I B
IB
D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D015152:Blotting, Northern; D002455:Cell Division; D005786:Gene Expression Regulation; D006649:Histocompatibility Antigens / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007700:Kinetics; D015458:Leukemia, T-Cell; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D011493:Protein Kinase C / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D006649:Histocompatibility Antigens; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019908:Proto-Oncogene Proteins c-raf; D011493:Protein Kinase C; D017493:Leukocyte Common Antigens; D013755:Tetradecanoylphorbol Acetate