Control of insulin receptor autophosphorylation by polypeptide substrates: inhibition and stimulation by interaction with the catalytic subunit.
Control of insulin receptor autophosphorylation by polypeptide substrates: inhibition and stimulation by interaction with the catalytic subunit.
复制标题
多肽底物对胰岛素受体自身磷酸化的控制：通过与催化亚基相互作用进行抑制和刺激。
DOI：
10.1021/bi00223a016
复制
发表时间：
1991
期刊：
影响因子：
2.9
通讯作者：
Schenker,E
中科院分区：
文献类型：
--
作者：
Kohanski,RA;Schenker,E
/* M insulin these peptides inhibited autophosphorylation. Stimulation was observed with reduced [iS-(carboxamidomethyl) cysteinyl] lysozyme (RCAM-lysozyme) and three peptides generated by CNBr cleavage, V8 proteinase digestion, and/or chemical modification. We also generated two peptide substrates from RCAM-lysozyme which did not stimulate receptor autophosphorylation and were very weak inhibitors. As a control peptide, the simple substrate angiotensin inhibited receptor autophosphorylation in the absence or presence of insulin. However, stimulatory peptide, but not insulin, significantly shifted the concentration dependence for inhibition by angiotensin. The stimulatory peptides also increased autophosphorylation of the cloned cytoplasmic domain of the kinase [R-BIRK; Villalba, M., Wente, S. R., Russell, D. S., Ahn, J., Reichelderfer, CF, & Rosen, O. M.(1989) Proc. Natl. Acad. Sci. USA 86, 7848]. Therefore, stimulation occurs by interactionwith the cytoplasmic process of the 8-subunit and not through interaction with the insulin binding a-subunit of the native receptor. Auto-phosphorylation was analyzed by mapping 32P-labeled tryptic phosphopeptides from the 8-subunit and fromR-BIRK. Nearlyidentical phosphopeptidemaps were found, comparing first, basal R-BIRK and basal native receptor, second, peptide-and insulin-stimulated native receptor, and third, peptide-stimulated R-BIRK and insulin-stimulated native receptor. Therefore, R-BIRK functions as a basal-state enzyme and can be stimulated in an insulin-like manner. On the basis of these observations, stimulation by insulin and by peptides yields similar functional results, but by apparentlydifferent mechanisms.
