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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Insulin / physiology*
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Meiosis / drug effects
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Models, Molecular
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Nitrogen Isotopes
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Nuclear Magnetic Resonance, Biomolecular / methods
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Oocytes / drug effects
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Oocytes / physiology
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Phosphorylation
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Protein Conformation
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Protein Structure, Tertiary
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Proteins / chemistry*
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Proteins / genetics
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Proteins / metabolism
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Proteins / pharmacology
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Receptor, Insulin / genetics
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Receptor, Insulin / physiology*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Xenopus Proteins*
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Xenopus laevis
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src Homology Domains
Substances
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Grb14 protein, Xenopus
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Insulin
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Nitrogen Isotopes
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Proteins
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Recombinant Fusion Proteins
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Xenopus Proteins
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Receptor, Insulin