| First Author | Tamemoto H | Year | 1994 |
| Journal | Nature | Volume | 372 |
| Issue | 6502 | Pages | 182-6 |
| PubMed ID | 7969452 | Mgi Jnum | J:21373 |
| Mgi Id | MGI:69362 | Doi | 10.1038/372182a0 |
| Citation | Tamemoto H, et al. (1994) Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1 [see comments]. Nature 372(6502):182-6 |
| abstractText | Insulin receptor substrate-1 (IRS-1) is the major substrate of insulin receptor and IGF-1 receptor tyrosine kinases; it has an apparent relative molecular mass of 160-190,000 (M(r), 160-190K) on SDS polyacrylamide gel. Tyrosine-phosphorylated IRS-1 binds the 85K subunit of phosphatidylinositol 3-kinase which may be involved in the translocation of glucose transporters and the abundant src homology protein (ASH)/Grb2 which may be involved in activation of p21ras and MAP kinase cascade. IRS-1 also has binding sites for Syp and Nck and other src homology 2 (SH2) signalling molecules. To clarify the physiological roles of IRS-1 in vivo, we made mice with a targeted disruption of the IRS-1 gene locus. Mice homozygous for targeted disruption of the IRS-1 gene were born alive but were retarded in embryonal and postnatal growth. They also had resistance to the glucose-lowering effects of insulin, IGF-1 and IGF-2. These data suggest the existence of both IRS-1-dependent and IRS-1-independent pathways for signal transduction of insulin and IGFs. |
