The PIR domain of Grb14 is an intrinsically unstructured protein: implication in insulin signaling

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• 作者：Moncoq ; Karine ; Broutin ; Isabelle ; Larue ; Valé ; ry ; Perdereau ; Dominique ; Cailliau ; Katia ; et. al.
• 关键词：Grb7 family ; Phosphorylated insulin receptor interacting region ; Signal transduction ; Unstructured protein ; BPS ; between PH and SH2 ; DTT ; dithiothreitol ; GVBD ; germinal vesicle breakdown ; HSQC ; heteronuclear single quantum correlation ; IGF-R ; insulin-like
• 刊名：FEBS Letters
• 出版年：2003
• 出版时间：November 20, 2003
• 年：2003
• 卷：554
• 期：3
• 页码：240-246
• 全文大小：319 K

文摘

Grb14 belongs to the Grb7 family of adapter proteins and was identified as a negative regulator of insulin signal transduction. Its inhibitory effect on the insulin receptor kinase activity is controlled by a newly discovered domain called PIR. To investigate the biochemical and biophysical characteristics of this new domain, we cloned and purified recombinant PIR-SH2, PIR, and SH2 domains. The isolated PIR and PIR-SH2 domains were physiologically active and inhibited insulin-induced reinitiation of meiosis in the Xenopus oocytes system. However, NMR experiments on ¹⁵N-labelled PIR revealed that it did not present secondary structure. These results suggest that the PIR domain belongs to the growing family of intrinsically unstructured proteins.