T cell activation and increases in protein kinase C activity enhance retinoic acid-induced gene transcription.
Retinoic acid (RA) has profound effects on cell growth and differentiation. Its receptors are members of the steroid/thyroid hormone receptor superfamily, which regulates nuclear transcription and gene expression by binding specific response elements. Protein kinase C (PKC) is activated during signal transduction initiated by a variety of membrane receptors. Using a RA-responsive element and reporter gene construct transfected into a T cell, we found: 1) T cell activation and PKC activators enhance transactivation by RA, 2) down-regulation of PKC protein has little effect on RA transactivation but abolishes superinduction by phorbol ester, which is restored by cotransfection of a PKC alpha-expression vector, and 3) cotransfection of dominant-negative c-jun does not prevent superinduction by phorbol ester. Together, these data demonstrate that PKC can modulate RA signal transduction, apparently without involvement of AP-1, and provide a new example of cross-talk between signal transduction pathways.
Yang
Y
Y
Laboratory of Immune Cell Biology, National Cancer Institute, Bethesda, Maryland 20892.
Minucci
S
S
Zand
D J
DJ
Ozato
K
K
Ashwell
J D
JD
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001483:Base Sequence; D017252:CD3 Complex / Q000276:immunology; D002460:Cell Line; D004357:Drug Synergism; D017930:Genes, Reporter; D016758:Genes, jun; D006825:Hybridomas; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*
D000906:Antibodies; D017252:CD3 Complex; D018808:Transcription Factor AP-1; D014212:Tretinoin; D008156:Luciferases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate