APS-mediated ubiquitination of the insulin receptor enhances its internalization, but does not induce its degradation.
APS-mediated ubiquitination of the insulin receptor enhances its internalization, but does not induce its degradation.
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DOI：
10.1507/endocrj.k06-056
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发表时间：
2007-02
影响因子：
2
通讯作者：
K. Kishi;K. Mawatari;Kikuko Sakai-Wakamatsu;T. Yuasa;Miao Wang;Makoto Ogura-Sawa;Y. Nakaya;S. Hatakeyama;Y. Ebina
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文献类型：
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作者：
K. Kishi;K. Mawatari;Kikuko Sakai-Wakamatsu;T. Yuasa;Miao Wang;Makoto Ogura-Sawa;Y. Nakaya;S. Hatakeyama;Y. Ebina
APS 是一种酪氨酸激酶衔接蛋白，具有 pleckstrin 同源性和 Src 同源性 2 结构域，在胰岛素刺激后被胰岛素受体激酶快速而强烈地酪氨酸磷酸化。我们之前已经证明，APS 基因敲除小鼠的胰岛素敏感性增加，这种增强可能是由于脂肪组织的胰岛素反应增加。然而，APS 在胰岛素信号传导中的功能迄今为止仍存在争议。在此，我们报告在过表达 IR 的 CHO 细胞中，APS 增强了胰岛素受体 (IR) 的配体依赖性多泛素化。 APS 介导的 IR 泛素化诱导 IR 内化增强，但不影响 IR 降解。这一发现显示了 APS 在胰岛素信号传导中的多效性功能之一。
APS, a tyrosine kinase adaptor protein with pleckstrin homology and Src homology 2 domains, is rapidly and strongly tyrosine-phosphorylated by insulin receptor kinase upon insulin stimulation. We have previously shown that APS knockout mice have increased insulin sensitivity, and that this enhancement is possibly due to increased insulin-response on adipose tissues. However, the function of APS in insulin signaling has so far been controversial. Here, we report that APS enhanced ligand-dependent multi-ubiquitination of the insulin receptor (IR) in CHO cells overexpressing the IR. APS-mediated ubiquitination of the IR induced enhancement of the IR internalization, but did not affect the IR degradation. This finding shows one of the pleiotropic functions of APS in insulin signaling.