Human insulin-like growth factor I receptor 950tyrosine is required for somatotroph growth factor signal transduction.

摘要: Insulin-like growth factor I (IGF-I), a hormone (GH)-dependent exerts feedback regulation of GH by inhibiting gene expression. IGF-I inhibition secretion is enhanced 3-5-fold in GC rat pituitary cells overexpressing the wild type 950Tyr human receptor which autophosphorylates appropriately. To determine critical amino acid sequence responsible for signaling, insertion, deletion, and site-directed mutants were constructed to substitute exon 16 beta-subunit transmembrane domain. All mutant transfectants bound with similar Kd untransfected but had markedly increased (7-34-fold) IGF-I-binding sites. responsiveness was tested transfectants. Overexpressed insertion receptors exhibited modest suppressive effect on response ligand, that observed cells. Deletion (IG-FIR delta 22) (amino 944-965) did not transduce signal gene. Site-directed therefore enhance endogenous receptor, unlike signal. transfectants, except deletion mutant, internalized radioactive ligand similarly required transduction somatotroph, IGF-I-mediated internalization.