Thyrotropin-releasing hormone rapidly activates protein phosphorylation in GH3 pituitary cells by a lipid-linked, protein kinase C-mediated pathway.

作者：Debra S. Drust, Thomas F.J. Martin · 发表于：Journal of Biological Chemistry · 年份：1984 · DOI：10.1016/s0021-9258(17)42631-7 · 被引用次数：115 · 研究领域：Growth Hormone and Insulin-like Growth Factors、Thyroid Disorders and Treatments、Neuropeptides and Animal Physiology

Thyrotropin-releasing hormone (TRH) is a tripeptide that rapidly enhances prolactin secretion in clonal, hormone-responsive GH3 rat pituitary cells. In an effort to identify postreceptor mechanisms for TRH, protein phosphorylation studies have been conducted. Our previous studies (Drust, D.S., Sutton, C.A., and Martin, T. F. J. (1982) J. Biol. Chem. 257, 3306-3312; Drust, D.S., and Martin, T. F. J. (1982) J. Biol. Chem. 257, 7566-7573) showed that TRH rapidly (less than 15 s) increased the phosphorylation of at least six cytosolic proteins (41K (Mr = 41,000), several 59K, 65K, 82K, and 97K) and, with a 5- to 10-min latency, increased the phosphorylation of a seventh (80K). Cyclic AMP did not appear to mediate TRH-stimulation of protein phosphorylation; in contrast, Ca2+ translocation and Ca2+-dependent protein phosphorylation accounted for hormone-induced changes in 97K (and possibly 41K) phosphorylation. The studies reported here indicate that lipid (diacylglycerol) accumulation and protein kinase C activation mediate TRH-stimulated phosphorylation of the additional five cytosolic proteins (two 59K, 65K, 80K, and 82K). This conclusion is based on the findings that: 1) phospholipase C treatment, which produces diacylglycerol, mimicked several TRH effects; 2) bombesin, another peptide that induces inositol phosphatide turnover, mimicked several TRH effects; 3) phorbol esters, which were shown to activate GH3 cell protein kinase C directly, produced TRH-like effects; 4) partial...