2007 Fiscal Year Final Research Report Summary
Novel Molecular Mechanisms Underlying Modulation of Insulin-Like Activities
| Project/Area Number |
16208028
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied animal science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAKAASHI Shin-ichiro The University of Tokyo, Graduate School of Agriculture and Life Sciences, Associate Professor (00197146)
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| Co-Investigator(Kenkyū-buntansha) |
HAKUNO Fumihiko The University of Tokyo, Graduate School of Agriculture and Life Sciences, Assistant Professor (30282700)
NAGATA Shinji The University of Tokyo, Graduate School of Agriculture and Life Sciences, Assistant Professor (40345179)
NISHIHARA Masugi The University of Tokyo, Graduate School of Agriculture and Life Sciences, Professor (90145673)
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| Project Period (FY) |
2004 – 2007
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| Keywords | insulin / insulin-like growth factor / signal transduction / insulin receptor substrates / tyrosine phosphorylation / two-hybrid screening / proteomics |
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| Research Abstract |
It is well known that phosphorylation of insulin receptor substrates (IRSs) by tyrosine kinases such as insulin-like growth factor (IGF)-I receptor and insulin receptor, mediate a variety of IGF/insulin bioactivities. In the present study, we found that IRSs form a high-molecular-mass complex (IRSomes) by interacting various proteins through phosphotyrosine-independent mechanism. We succeeded to identify over 20 kinds of proteins (IRS-associated proteins; IRSAPs) forming IRSomes, were identified by yeast two-hybrid screening using IRSs cDNAs as a bait or proteomics analysis of proteins in the co-immunoprecipitates using anti-IRSs antibodies. These proteins were categorized as sorters that transport IRSs to appropriate intercellular sites, mediators that mediate IGF/insulin activities and modulators that modulate their activities. Overexpression or knock-down of these IRSAPs in various cell types enhanced or depressed IGF/insulin bioactivities and other extracellular factors affect binding of IRS to IRSAP. Our results demonstrated that IRSomes play important roles to modulate insulin-like activities under various physiological conditions.
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Research Products
(116 results)
