Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor
Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor
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DOI：
10.1006/bbrc.2000.3762
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发表时间：
2000-11-11
影响因子：
3.1
通讯作者：
Nissley, P
中科院分区：
文献类型：
--
作者：
Dey, BR;Furlanetto, RW;Nissley, P
SOCS蛋白是一类通过Janus激酶（JAK）/信号转导子和转录激活子（STAT）途径作为细胞因子受体信号传导的负调节剂的蛋白。在酵母双杂交筛选的人胎脑文库中，我们先前已经确定SOCS-2作为激活的IGF-I受体（IGFIR）的结合伴侣。为了测试SOCS-3是否也与IGFIR结合，我们通过逆转录-聚合酶链反应从人骨骼肌mRNA中克隆了人SOCS-3。SOCS-3 mRNA在人胚胎和成人组织中均有表达，在人癌细胞系（Hela、A549肺腺癌和G361人黑色素瘤）中也有表达。我们发现，人SOCS-3蛋白直接与激活的IGFIR和胰岛素受体（IR）的细胞质结构域在酵母双杂交试验。在使用来自哺乳动物细胞的IGFIR的GST-SOCS-3下拉实验中，以及在IGFIR和FLAG-SOCS-3在人胚肾293细胞中瞬时表达的免疫沉淀实验中，我们发现SOCS-3在体外和完整细胞中与IGFIR组成型相互作用。与SOCS-2不同，hSOCS-3在293细胞中加入IGF-I后，酪氨酸磷酸化。我们的结论是，SOCS-3结合IGFIR，并可能是受体酪氨酸激酶的直接底物。(C)北京大学出版社.
SOCS proteins are a class of proteins that are negative regulators of cytokine receptor signaling via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. In a yeast two-hybrid screen of a human fetal brain library, we have previously identified SOCS-2 as a binding partner of the activated IGF-I receptor (IGFIR). To test whether or not SOCS-3 also binds to the IGFIR, we cloned human SOCS-3 by reverse transcription-polymerase chain reaction from human skeletal muscle mRNA. SOCS-3 mRNA was expressed in many human fetal and adult tissues and in some human cancer cell lines (Hela, A549 pulmonary adenocarcinoma and G361 human melanoma). We found that human SOCS-3 protein interacts directly with the cytoplasmic domains of the activated IGFIR and the insulin receptor (IR) in the yeast two-hybrid assay. In GST-SOCS-3 pull-down experiments using IGFIR from mammalian cells and in immunoprecipitation experiments in which IGFIR and FLAG-SOCS-3 were transiently expressed in human embryonic kidney 293 cells, we found that SOCS-3 interacts constitutively with IGFIR in vitro and in intact cells. Unlike SOCS-2, hSOCS-3 was phosphorylated on tyrosines in response to IGF-I addition to 293 cells. We conclude that SOCS-3 binds to the IGFIR and may be a direct substrate for the receptor tyrosine kinase. (C) 2000 Academic Press.