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Research Article Free access | 10.1172/JCI119246

The adapter protein Grb10 associates preferentially with the insulin receptor as compared with the IGF-I receptor in mouse fibroblasts.

L Laviola, F Giorgino, J C Chow, J A Baquero, H Hansen, J Ooi, J Zhu, H Riedel, and R J Smith

Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

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Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

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Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

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Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

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Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

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Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

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Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

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Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

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Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

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Published March 1, 1997 - More info

Published in Volume 99, Issue 5 on March 1, 1997
J Clin Invest. 1997;99(5):830–837. https://doi.org/10.1172/JCI119246.
© 1997 The American Society for Clinical Investigation
Published March 1, 1997 - Version history
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Abstract

To identify receptor-associated proteins that may contribute to the specificity of insulin and IGF-I signaling responses, a mouse embryo library was screened using the yeast two-hybrid system. Multiple receptor-interactive clones encoding the SH2 domain of the adapter protein Grb10 were isolated. Subsequent cloning of the full-length Grb10 sequence from a mouse fat cDNA library defined a previously unknown Grb10 variant, that appears to be the predominant isoform in mouse tissues. Receptor-deficient R- cells (fibroblasts from mice with homologous disruption of the IGF-I receptor gene) and transfected R- cells expressing either insulin receptors (R-IR cells) or IGF-I receptors (R+ cells) were used to investigate the specificity of Grb10 interaction with the two related receptors. Hormone-activated insulin receptors in R-IR cells coprecipitated with three species, all recognized as Grb10 isoforms by specific Grb10 antibody. Under the same conditions, Grb10 was essentially undetectable in IGF-I receptor immunoprecipitates from stimulated R+ cells. Grb10 association with insulin receptors was maximal at 10 nM insulin stimulation and sustained from 5-10 min after hormone stimulation in R-IR cells. In conclusion, Grb10 interacts preferentially with insulin vs. IGF-I receptors in intact cells and, thus, may have a role in mediating insulin receptor-specific cellular responses.

Version history
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