Insulin receptor-related receptor is expressed in pancreatic beta-cells and stimulates tyrosine phosphorylation of insulin receptor substrate-1 and -2.
Insulin receptor-related receptor is expressed in pancreatic beta-cells and stimulates tyrosine phosphorylation of insulin receptor substrate-1 and -2.
复制标题
胰岛素受体相关受体在胰腺β细胞中表达，并刺激胰岛素受体底物-1和-2的酪氨酸磷酸化。
作者：
I. Hirayama;H. Tamemoto;H. Yokota;S. Kubo;J. Wang;H. Kuwano;Y. Nagamachi;T. Takeuchi;T. Izumi
筛选小鼠胰岛中的受体型蛋白酪氨酸激酶，以鉴定胰腺β细胞中可能的生长/分化因子。分析显示，胰岛素受体相关受体（IRR）在胰岛以及来自转基因小鼠的几种高度分化的β细胞系中高度表达。与β细胞系中加工形式的IRR相比，胰岛主要含有未切割的前受体IRR，这表明IRR的活性受到体内加工蛋白酶水平的调节。为了检查IRR信号通路，在中国仓鼠卵巢细胞中表达了由胰岛素受体胞外结构域和IRR胞内结构域组成的嵌合受体。混合受体具有功能性，因为胰岛素能够使这些细胞中的催化结构域酪氨酸磷酸化。它还刺激胰岛素受体底物 (IRS)-1 和 IRS-2 的酪氨酸磷酸化，表明这两种蛋白都是完整细胞中 IRR 蛋白酪氨酸激酶的底物。最近报道的 IRS-2 敲除小鼠的表型表明，IRS-2 介导的信号通路控制胰岛素抵抗状态下胰腺 β 细胞质量的代偿性增加。根据我们对 IRR 的特异性表达及其向 IRS-2 发出信号的能力的发现，我们推测该受体可能在 β 细胞质量的调节中发挥作用。
The receptor-type protein tyrosine kinases in murine pancreatic islets were screened to identify possible growth/differentiation factors in pancreatic beta-cells. The analysis revealed that insulin receptor-related receptor (IRR) is highly expressed in the islets as well as in several highly differentiated beta-cell lines derived from transgenic mice. Islets predominantly contain IRR as uncleaved proreceptors compared with IRR as processed forms in the beta-cell lines, suggesting that the activity of IRR is regulated on the level of processing proteases in vivo. To examine the IRR signaling pathway, a chimeric receptor consisting of the extracellular domain of insulin receptor and the intracellular domain of IRR was expressed in Chinese hamster ovary cells. The hybrid receptor is functional because insulin is capable of tyrosine-phosphorylating the catalytic domain in these cells. It also stimulates the tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2, indicating that both proteins serve as substrates of IRR-protein tyrosine kinase in intact cells. The phenotype of the IRS-2 knockout mouse recently reported suggests that an IRS-2-mediated signaling pathway controls the compensatory increase in pancreatic beta-cell mass in insulin-resistant states. From our findings of the specific expression of IRR and its ability of signaling to IRS-2, we speculate that this receptor might play a role in the regulation of beta-cell mass.