ERBB3 IS INVOLVED IN ACTIVATION OF PHOSPHATIDYLINOSITOL 3-KINASE BY EPIDERMAL GROWTH-FACTOR
ERBB3 IS INVOLVED IN ACTIVATION OF PHOSPHATIDYLINOSITOL 3-KINASE BY EPIDERMAL GROWTH-FACTOR
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DOI：
10.1128/mcb.14.6.3550
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发表时间：
1994-06-01
影响因子：
5.3
通讯作者：
CANTLEY, LC
中科院分区：
文献类型：
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作者：
SOLTOFF, SP;CARRAWAY, KL;CANTLEY, LC
关于表皮生长因子（EGF）受体与磷脂酰肌醇（PtdIns）3-激酶结合和/或激活磷脂酰肌醇（PtdIns）3-激酶的能力的证实结果已经发表。尽管EGF的能力，刺激生产的PtdIns 3-激酶产品，并导致PtdIns 3-激酶活性的外观在抗磷酸酪氨酸免疫沉淀在几个细胞系，我们没有检测到EGF刺激的PtdIns 3-激酶活性的抗EGF受体免疫沉淀。该结果与该受体序列中缺乏磷酸化Tyr-X-X-Met基序，即p85 Src同源性2（SH 2）结构域识别序列一致。EGF受体同源物ErbB 2蛋白也缺乏这种基序。然而，ErbB 3蛋白在羧基末端独特结构域中具有七个重复的Tyr-X-X-Met基序。在这里，我们表明，在A431细胞，表达EGF受体和ErbB 3，PtdIns 3-激酶共沉淀与ErbB 3蛋白（p180（erbB 3））在EGF的反应。p180（erbB 3）也被证明是酪氨酸磷酸化，以响应EGF。相反，在某些细胞（PC 12和A549细胞）中，EGF激活PtdIns 3-激酶的不同机制。因此，我们第一次表明，ErbB 3可以介导EGF反应的细胞表达ErbB 3和EGF受体。
Conflicting results concerning the ability of the epidermal growth factor (EGF) receptor to associate with and/or activate phosphatidylinositol (PtdIns) 3-kinase have been published. Despite the ability of EGF to stimulate the production of PtdIns 3-kinase products and to cause the appearance of PtdIns 3-kinase activity in antiphosphotyrosine immunoprecipitates in several cell lines, we did not detect EGF-stimulated PtdIns 3-kinase activity in anti-EGF receptor immunoprecipitates. This result is consistent with the lack of a phosphorylated Tyr-X-X-Met motif, the p85 Src homology 2 (SH2) domain recognition sequence, in this receptor sequence. The EGF receptor homolog, ErbB2 protein, also lacks this motif. However, the ErbB3 protein has seven repeats of the Tyr-X-X-Met motif in the carboxy-terminal unique domain. Here we show that in A431 cells, which express both the EGF receptor and ErbB3, PtdIns 3-kinase coprecipitates with the ErbB3 protein (p180(erbB3)) in response to EGF. p180(erbB3) is also shown to be tyrosine phosphorylated in response to EGF. In contrast, a different mechanism for the activation of PtdIns 3-kinase in response to EGF occurs in certain cells (PC12 and A549 cells). Thus, we show for the first time that ErbB3 can mediate EGF responses in cells expressing both ErbB3 and the EGF receptor.