Jui H Y, Accili D, Taylor S I
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 20892-1770, USA.
Biochemistry. 1996 Nov 12;35(45):14326-30. doi: 10.1021/bi9613032.
In many tissues, the insulin receptor-related receptor (IRR) is colocalized with the homologous receptors for insulin and insulin-like growth factor-I (IGF-I). Since a ligand for the IRR has not yet been identified, it has been proposed previously that IRR may be activated and transduce its signal via formation of hybrids with the insulin and IGF-I receptors. To test this hypothesis, we have coexpressed the human IRR and the human insulin receptor (IR) in NIH-3T3 cells. Although IRR/IR hybrid receptors were detected in these cells by using immunoprecipitation techniques, only a small proportion of each receptor was assembled into hybrids. While insulin was capable of stimulating insulin receptors autophosphorylation in these cells, there was no detectable increase in the total phosphotyrosine content of IRR. We conclude that the IRR/IR hybrid receptor does not play a major role in IRR signal transduction in response to insulin in NIH-3T3-hIRR/hIR cells.
在许多组织中,胰岛素受体相关受体(IRR)与胰岛素及胰岛素样生长因子-I(IGF-I)的同源受体共定位。由于尚未鉴定出IRR的配体,此前有人提出IRR可能通过与胰岛素和IGF-I受体形成杂合体而被激活并转导其信号。为了验证这一假设,我们在NIH-3T3细胞中共表达了人IRR和人胰岛素受体(IR)。尽管通过免疫沉淀技术在这些细胞中检测到了IRR/IR杂合受体,但每种受体中只有一小部分组装成了杂合体。虽然胰岛素能够刺激这些细胞中胰岛素受体的自身磷酸化,但IRR的总磷酸酪氨酸含量没有可检测到的增加。我们得出结论,在NIH-3T3-hIRR/hIR细胞中,IRR/IR杂合受体在响应胰岛素的IRR信号转导中不发挥主要作用。