Signal transduction mechanism of insulin and insulin-like growth factor-1.
Insulin and insulin-like growth factor-1 (IGF-1) are two structurally related hormones which produce similar biological activities such as metabolic and growth promoting actions. Their receptors, insulin and IGF-1 receptors, also share similarities in both structure and functions such as tyrosine-specific protein kinase. We identified insulin receptor substrate-1 (IRS-1) as a common substrate for insulin and IGF-1 receptor tyrosine kinases. We generated IRS-1 knockout mice and showed that IRS-1 plays a physiological role in signal transduction and biological actions of insulin and IGF-1. We also identified pp190 (IRS-2) as an alternative substrate for IRS-1.
Kadowaki
T
T
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Tobe
K
K
Honda-Yamamoto
R
R
Tamemoto
H
H
Kaburagi
Y
Y
Momomura
K
K
Ueki
K
K
Takahashi
Y
Y
Yamauchi
T
T
Akanuma
Y
Y
Yazaki
Y
Y
D000818:Animals; D006130:Growth Disorders / Q000209:etiology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D010750:Phosphoproteins / Q000172:deficiency / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction
C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin