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The PIR domain of Grb14 is an intrinsically unstructured protein: implication in insulin signaling
Author(s) -
Moncoq Karine,
Broutin Isabelle,
Larue Valéry,
Perdereau Dominique,
Cailliau Katia,
Browaeys-Poly Edith,
Burnol Anne-Françoise,
Ducruix Arnaud
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01095-0
Subject(s) - xenopus , insulin receptor , sh2 domain , insulin , microbiology and biotechnology , biology , signal transduction , insulin receptor substrate , regulator , signal transducing adaptor protein , recombinant dna , biochemistry , chemistry , proto oncogene tyrosine protein kinase src , gene , endocrinology , insulin resistance
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.