Interleukin 1 induces early protein phosphorylation and requires only a short exposure for late induced secretion of beta-endorphin in a mouse pituitary cell line.
Previous work has shown that prolonged pretreatment of a mouse anterior pituitary cell line, AtT-20 cells, with the cytokine interleukin 1 (IL-1) stimulates beta-endorphin release and potentiates the secretion induced by many secretagogues. Desensitization of protein kinase C (PKC) by pretreatment with phorbol ester [phorbol 12-tetradecanoate 13-acetate (TPA)] for 8 hr abolished the secretion induced by TPA as well as the enhancement of TPA-induced beta-endorphin release produced by IL-1. Desensitization of PKC only partly abolished the potentiating effects of IL-1 on corticotropin-releasing factor-induced beta-endorphin secretion. In contrast, IL-1-induced beta-endorphin release was independent of PKC. We observed that treatment of AtT-20 cells with IL-1 markedly phosphorylated 19-, 20-, and 60-kDa proteins within minutes, presumably by early activation of protein kinases. Prolonged treatment with TPA, which was shown to desensitize an 87-kDa protein (a substrate for PKC), had no effect on IL-1-induced phosphorylation of 20-, 60-, and 87-kDa proteins, indicating that the phosphorylation of these proteins does not involve PKC. IL-1 does not generate cAMP in AtT-20 cells, suggesting that a cAMP-dependent protein kinase is also not involved. Prolonged treatment with IL-1 abolishes the capacity of cytokine to induce the phosphorylation of 20- and 60-kDa proteins. The presence of IL-1 was required initially only for a short time to induce late secretion in AtT-20 cells. These observations indicate that once IL-1 generates an early signal, its presence is no longer necessary for the subsequent secretion of beta-endorphin.
Făgărăşan
M O
MO
Laboratory of Cellular Biology, National Institute of Mental Health, Bethesda, MD 20892.
Bishop
J F
JF
Rinaudo
M S
MS
Axelrod
J
J
D000818:Animals; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010750:Phosphoproteins / Q000302:isolation & purification; D010766:Phosphorylation; D010903:Pituitary Gland, Anterior; D010911:Pituitary Neoplasms; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D001615:beta-Endorphin / Q000096:biosynthesis* / Q000378:metabolism
D007375:Interleukin-1; D009363:Neoplasm Proteins; D010710:Phosphates; D010750:Phosphoproteins; D001615:beta-Endorphin; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate