Role of protein kinase C in IFN-mediated Ly-6E antigen induction.
The YAC T cell lymphoma normally does not express Ly-6E mRNA or Ly-6E surface molecules but can be induced to do so on incubation with either IFN-gamma or IFN-alpha/beta. This system afforded a model to assess the possible role of protein kinase C (PKC) in IFN-mediated Ly-6E induction. First, we used various pharmacologic agents known to interfere with the function of PKC or other kinases. The PKC inhibitors H-7 and phloretin were found to block Ly-6E induction by IFN-gamma or IFN-alpha/beta both at the mRNA and protein levels. In contrast, inhibitors of cyclic nucleotide-dependent kinases (HA1004), of myosin L chain kinase (ML-9, A-3) or of calmodulin (R24157, W-7) failed to suppress this induction. Next, we investigated the effects of the PKC activators PMA and mezerein (MEZ) on Ly-6E expression. Although neither PMA nor MEZ by themselves could induce Ly-6E in YAC cells, both agents enhanced by up to fivefold the induction of Ly-6 mRNA and Ly-6E surface expression triggered by IFN-gamma. However, the induction of Ly-6E expression caused by IFN-alpha/beta was only marginally increased by cotreatment of YAC cells with PMA or MEZ. Altogether, these observations demonstrate that PKC or a related kinase is involved in the transduction mechanisms that lead to Ly-6E induction. However, activation of PKC is not sufficient for this induction and requires other unidentified signal(s) provided by IFN. Our data also indicate that IFN-gamma and IFN-alpha/beta induce Ly-6E through overlapping but distinct intracellular pathways with different sensitivities to PKC activators.
Department of Immunology Research, Merck, Sharp and Dohme Research Laboratories, Rahway, NJ 07065.
F J
FJ
Dumont
A
A
Altmeyer
M J
MJ
Staruch
R
R
Dijkmans
R G
RG
Palfree
P A
PA
Fischer
D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis* / Q000235:genetics; D000954:Antigens, Surface / Q000235:genetics; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology; D002460:Cell Line; D004224:Diterpenes; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D007372:Interferons / Q000494:pharmacology*; D051379:Mice; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018800:Thy-1 Antigens; D013997:Time Factors
D000950:Antigens, Ly; D000954:Antigens, Surface; D002147:Calmodulin; D004224:Diterpenes; D012333:RNA, Messenger; D013729:Terpenes; D018800:Thy-1 Antigens; C011309:mezerein; D007372:Interferons; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate