| Budget Amount *help |
¥47,450,000 (Direct Cost: ¥36,500,000、Indirect Cost: ¥10,950,000)
Fiscal Year 2007: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2006: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2005: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
Fiscal Year 2004: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
|
|---|
| 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.
|
