Evidence that the activation of an inactive pool of membrane-associated protein kinase C is linked to the IL-2-dependent survival of T lymphocytes.
The activation of protein kinase C (PKC) is believed to result from the translocation of inactive cytosolic enzyme to the lipid environment of membranes. However, by using a novel method for measuring PKC activity directly in isolated membranes, we have previously shown that a significant proportion of the PKC present in a variety of cells associates with membranes in an inactive state, and that this pool of inactive PKC can be stimulated specifically in cells in the absence of translocation. IL-2 did not stimulate the translocation of PKC to membranes in the IL-2-dependent mouse T cell line, CTLL-2. Nevertheless, a transient, two approximately threefold increase in membrane PKC activity was observed within 10 min of IL-2 addition to these cells. This increase was entirely caused by the activation of a pool of inactive membrane PKC previously associated with the membrane. The inhibition of PKC activity by the specific inhibitors bisindolylmaleimide (BIS) and 1-O-hexadecyl-2-O-methyl-rac-glycerol (AMG) blocked the ability of IL-2 to suppress the onset of apoptosis in IL-2 and serum-deprived CTLL-2 cells. The inhibition of this important function of IL-2 was most pronounced when the PKC inhibitors were added to the medium within 2 h of stimulating the cells with IL-2. The results suggest that transient activation of inactive membrane PKC is linked to the IL-2 receptor signaling, and may be an important step in the mechanism(s) by which the cytokine suppresses cell death in T lymphocytes.
Lu
Y
Y
Institute for Biological Sciences, National Research Council of Canada, Ottawa.
Tremblay
R
R
Jouishomme
H
H
Chakravarthy
B
B
Durkin
J P
JP
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D002470:Cell Survival; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*; D013997:Time Factors
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011493:Protein Kinase C