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

[摘要]

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.

[学科分类] 生物化学/生物物理

[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 growth factor receptor;IR;insulin receptor;IUP;intrinsically unstructured protein;PH;pleckstrin homology;PIR;phosphorylated insulin receptor interacting region;PKCζ;protein kinase Cζ;SH2;Src homology 2;ZIP;protein kinase Cζ interacting protein