IGF-I receptor signalling: lessons from the somatotroph.

摘要: Insulin-like growth factor 1 (IGF-I) is a major feedback regulator of pituitary GH secretion, with defined actions occurring at both the hypothalamus and pituitary. The IGF-I gene expressed in anterior GH-dependent manner thus providing for endocrine-as well as autocrine-mediated regulation. In turn, selectively specifically inhibits transcription its attenuating effects on nascent mRNA synthesis being demonstrable within h. Binding to cell surface receptor followed by rapid activation intrinsic tyrosine kinase activity beta-subunit phosphorylation insulin substrate (IRS-1). Structure-function studies human were performed stable, GH-secreting transfectants expressing either cDNA encoding wild-type (WT) IGF exhibiting enhanced responsiveness, or cDNAs mutants truncated, kinase-deficient (952STOP). 950Tyr situated submembrane domain was found be critical transducing signal gene. failed suppress secretion signalling endogenous rat receptors when hybrid formed hemi-receptors. This dominant negative effect hormone also evidenced mitogenic signals blocked vitro vivo these receptors. Using similar doses IGF-I, demonstrated ligand-dependent ERKs cells. conclusion, mediates regulation GH. Thus, mass may determine responses malnutrition, pregnancy, refeeding. mutations prove useful abrogate IGF-I-dependent tumors. These structure-function provide mechanistic insights into metabolic control axis, target tissue proliferative characteristics.