First Author | Sun XJ | Year | 1995 |
Journal | Nature | Volume | 377 |
Issue | 6545 | Pages | 173-7 |
PubMed ID | 7675087 | Mgi Jnum | J:38317 |
Mgi Id | MGI:85693 | Doi | 10.1038/377173a0 |
Citation | Sun XJ, et al. (1995) Role of IRS-2 in insulin and cytokine signalling. Nature 377(6545):173-7 |
abstractText | The protein IRS-1 acts as an interface between signalling proteins with Src-homology-2 domains (SH2 proteins) and the receptors for insulin, IGF-1, growth hormone, several interleukins (IL-4, IL-9, IL-13) and other cytokines. It regulates gene expression and stimulates mitogenesis, and appears to mediate insulin/IGF-1-stimulated glucose transport. Thus, survival of the IRS-1-/- mouse with only mild resistance to insulin was surprising. This dilemma is provisionally resolved with our discovery of a second IRS-signalling protein. We purified and cloned a likely candidate called 4PS from myeloid progenitor cells and, because of its resemblance to IRS-1, we designate it IRS-2. Alignment of the sequences of IRS-2 and IRS-1 revealed a highly conserved amino terminus containing a pleckstrin-homology domain and a phosphotyrosine-binding domain, and a poorly conserved carboxy terminus containing several tyrosine phosphorylation motifs. IRS-2 is expressed in many cells, including tissues from IRS-1-/- mice, and may be essential for signalling by several receptor systems. |