Role of protein kinase c in interleukin 1, anti‐T3, and mitogenic lectin‐induced interleukin 2 secretion

Abstract

Activation of T-lymphocytes by antigen, mitogenic lectins, or antibodies against the T-cell receptor complex, particularly in the presence of IL1, induces the secretion of the T-cell growth factor IL2. IL2 then has a major role in regulating the duration and magnitude of the immune response. Interaction of antigen, antibodies against the T-cell receptor complex, or mitogenic lectins with T-lymphocytes also induces hydrolysis of membrane phospholipids, leading to the production of diacylglycerol, an activator of the Ca2+- and phospholipid-dependent phosphotransferase, protein kinase C (PKC). Phorbol esters, potent activators of PKC, augment secretion of the T-cell growth factor, interleukin 2 (IL2). Activation of PKC may therefore serve as an important early event in the production and secretion of IL2. We have determined whether IL2 secretion can be induced in the murine cell T-lymphocyte line LBRM 331A5, where PKC is inhibited by staurosporine or sphingosine or in cells where PKC is depleted by prolonged incubation with high concentrations of phorbol esters. In cells in which PKC was either inhibited or depleted, antibodies against the T3 portion of the T-cell receptor complex and the mitogenic lectin phytohemagglutinin (PHA) still triggered IL2 secretion. In addition, the monokine IL1 augmented this IL2 secretion irrespective of whether PKC was inhibited or depleted. These data indicate that activation of PKC is not an obligatory step for IL2 secretion in LBRM 331A5 murine T-lymphocytes.

Lysophospholipids activate ovarian and breast cancer cells

“…Phorbol esters, probably through activation of protein kinase C family members, prevent increases in [Ca2+]1 induced by activation of a number of different cell-surface receptors [30]. This provides further support that LPA, LPS and SPC increase [Ca2+]1 in ovarian cancer cells by interacting with a specific cell-surface receptor(s).…”

“…These lysophospholipids completely desensitize each other in calcium release, suggesting that they either share a common receptor or that their downstream signalling pathways interact or converge. This is supported by the ability of lanthanum (which does not penetrate the cell membrane [10]) and phorbol esters (which have been shown to desensitize receptor-mediated effects in other systems [30]) to prevent increases in [Ca2+] induced by LPA, LPS and SPC. The ability of LPG to competitively inhibit LPA, but not LPS or SPC, suggests that LPA binds to an independent receptor(s) from LPS and SPC.…”

“…In our studies, treatment with PTX did not significantly inhibit EGF-induced cellular proliferation under conditions where it inhibited LPA-induced proliferation (data not shown), indicating a lack of non-specific effect of PTX (data not shown). The relatively non-specific kinase inhibitor staurosporin (1,M) [30,33] also markedly inhibits LPA-induced proliferation, indicating that intracellular kinase activity is required for the mitogenic activity of LPA ( Table 2).…”

Exocytosis in neurohypophysial nerve terminals is not coupled to protein kinase C translocation

“…In addition, although the former study [20] advances an argument for strong OT release by activation of PKC, the other [21] In conclusion, we have strong evidence to suggest that exocytosis in neurohypophysial nerve terminals is not directly mediated by PKC activation. This is in accord with the data favouring the occurrence of exocytosis independent of PKC activation in a variety of systems, including luteinizing-hormone release from pituitary gonadotropes [23], secretion of interleukin-2 in lymphocytes [24], and insulin secretion from permeabilized RIN m5F cells challenged with GTP analogues in the absence of Ca2+ [10].…”

Glycobiology of Signal Transduction

“…It has been shown that the cross-linking of Lselectin and Mac-1, a PZintegrin, induces O,*-tion of phospholipase C takes place with the subsequent production of diacylglycerols, activators of some types of protein kinase C, and Ins-1,4,5-P3, involved in the activation of Ca2+-channels that transiently increases the cytosolic concentration of this cation. However, the activation of protein kinase C does not appear to be an obligatory step in the production of IL-2 by Tlymphocytes (Mills et al, 1989). The concanavalin A-induced turnover of PtdIns-4,5-P2, IL-2 production, and DNA synthesis in lymphocytes is potentiated by macrophages.…”