ROLE OF IRS-2 IN INSULIN AND CYTOKINE SIGNALING

被引:756
作者
SUN, XJ
WANG, LM
ZHANG, YT
YENUSH, L
MYERS, MG
GLASHEEN, E
LANE, WS
PIERCE, JH
WHITE, MF
机构
[1] HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215
[2] HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215
[3] NIH,CELL & MOLEC BIOL LAB,BETHESDA,MD 20892
[4] HARVARD UNIV,DEPT MOLEC & CELLULAR BIOL,HARVARD MICROCHEM FACIL,CAMBRIDGE,MA 02138
关键词
D O I
10.1038/377173a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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(1-7). It regulates gene expression acid stimulates mitogenesis, and appears to mediate insulin/IGF-1-stimulated glucose transport(8). Thus, survival of the IRS-1(-/-) mouse with only mild resistance to insulin was surprising(9,10). 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 acid 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(11), and may be essential for signalling by several receptor systems.
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页码:173 / 177
页数:5
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