Related Experiment Video
Updated: Aug 30, 2026

Precise Visualization of Insulin Receptors A and B in Murine Brain with an RNA In Situ Hybridization Assay
Published on: July 15, 2025
The PIR domain of Grb14 is an intrinsically unstructured protein: implication in insulin signaling
Karine Moncoq1, Isabelle Broutin, Valéry Larue
1Laboratoire de Cristallographie et RMN Biologiques, Faculté de Pharmacie Paris 5, 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France.
Abstract:
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 (15)N-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.
Related Concept Videos
Insulin: The Receptor and Signaling Pathways
Assembly of Signaling Complexes
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
The JAK-STAT Signaling Pathway
PI3K/mTOR/AKT Signaling Pathway
Regulation of the Unfolded Protein Response
IP3/DAG Signaling Pathway
