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在 INS-1E 胰岛β细胞中,通过诱导型 CSF1R/IRR 受体构建体激活 Erk1/2 磷酸化,但不激活 Akt/Pkb。

Activation of Erk1/2 phosphorylation but not of Akt/Pkb through an inducible CSF1R/IRR-receptor construct in INS-1E beta-cells.

机构信息

Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.

出版信息

Arch Physiol Biochem. 2010 Jul;116(3):128-36. doi: 10.3109/13813455.2010.494671.

Abstract

CONTEXT

The insulin receptor-related receptor (IRR) is an orphan receptor belonging to the insulin receptor (IR) family. Despite its unknown function, the specific tissue expression and the high sequence homology with the IR and the insulin-like growth factor 1 receptor (IGF1R) suggest a biological role in beta-cells.

OBJECTIVES

In this study we investigated the influence of a stimulatable IRR-tyrosine kinase on major IR/IGF1R signaling pathways and on proliferation and apoptosis of INS-1E beta-cells.

METHODS

INS-1E cells were stably transfected with a colony stimulating factor 1 receptor (CSF1R)/IRR construct activated by a macrophage colony stimulating factor.

RESULTS AND CONCLUSION

After stimulation the construct showed time and dose dependent autophosphorylation and transient extracellular signal regulated kinase 1/2 activation. Protein kinase b was not phosphorylated and also an effect on proliferation and apoptosis of INS-1E could not be demonstrated. Thus, no obvious biologic function of the IRR is present in INS-1E beta-cells.

摘要

背景

胰岛素受体相关受体(IRR)是一种孤儿受体,属于胰岛素受体(IR)家族。尽管其功能未知,但它在特定组织中的表达和与 IR 和胰岛素样生长因子 1 受体(IGF1R)的高度序列同源性表明其在β细胞中具有生物学作用。

目的

本研究旨在探讨可诱导的 IRR-酪氨酸激酶对主要的 IR/IGF1R 信号通路以及 INS-1E 胰岛β细胞增殖和凋亡的影响。

方法

使用集落刺激因子 1 受体(CSF1R)/IRR 构建体稳定转染 INS-1E 细胞,该构建体可被巨噬细胞集落刺激因子激活。

结果和结论

刺激后,构建体表现出时间和剂量依赖性的自身磷酸化和短暂的细胞外信号调节激酶 1/2 激活。蛋白激酶 b 未磷酸化,也未证明对 INS-1E 增殖和凋亡有影响。因此,IRR 在 INS-1E 胰岛β细胞中没有明显的生物学功能。

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