A novel PKC regulates ERK activation and degranulation of cytotoxic T lymphocytes: Plasticity in PKC regulation of ERK.
Stimulation of cytotoxic T lymphocyte (CTL) degranulation with plate-bound anti-CD3 Ab leads to two phases of ERK activation: an early PKC-independent phase followed by a later sustained PKC-dependent phase. Herein, we show that a novel PKC (nPKC) mediates the late phase of ERK activation, upstream of Ras in murine T cells. In contrast, when CTL are activated with cross-linked anti-CD3 Ab, which does not trigger CTL degranulation, there is a requirement for conventional PKC (cPKC) for ERK activation. We detect increased novel PKCtheta activation only when CTL are stimulated with plate-bound Ab and not cross-linked Ab. Interestingly, in T cells from mice lacking PKCtheta, sustained ERK activation requires the activity of cPKC, implying that PKCtheta is required for the nPKC pathway that normally mediates sustained ERK activation. CTL lines derived from PKCtheta-deficient mice degranulate and activate ERK normally, and exhibit altered expression of PKC isozymes, which may compensate for the loss of PKCtheta. Taken together, these data demonstrate that normally an nPKC participates in the sustained activation of ERK. However, if the nPKC pathway is compromised, alternate PKC pathways can compensate, suggesting that considerable plasticity exists with respect to PKC regulation of ERK activation in T cells.
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Lawrence G
LG
Puente
Jin-Shu
JS
He
Hanne L
HL
Ostergaard
D000818:Animals; D015153:Blotting, Western; D004789:Enzyme Activation / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D011493:Protein Kinase C / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology*
D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases