The PIR domain of Grb14 is an intrinsically unstructured protein: implication in insulin signaling.
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.
Moncoq
Karine
K
Laboratoire de Cristallographie et RMN Biologiques, Faculté de Pharmacie Paris 5, 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France.
Broutin
Isabelle
I
Larue
Valéry
V
Perdereau
Dominique
D
Cailliau
Katia
K
Browaeys-Poly
Edith
E
Burnol
Anne-Françoise
AF
Ducruix
Arnaud
A
D000818:Animals; D007328:Insulin / Q000502:physiology*; D008540:Meiosis / Q000187:drug effects; D008958:Models, Molecular; D009587:Nitrogen Isotopes; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D011972:Receptor, Insulin / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D029867:Xenopus Proteins; D014982:Xenopus laevis; D018909:src Homology Domains
C490978:Grb14 protein, Xenopus; D007328:Insulin; D009587:Nitrogen Isotopes; D011506:Proteins; D011993:Recombinant Fusion Proteins; D029867:Xenopus Proteins; D011972:Receptor, Insulin