Identification of a new adapter protein that may link the common beta subunit of the receptor for granulocyte/macrophage colony-stimulating factor, interleukin (IL)-3, and IL-5 to phosphatidylinositol 3-kinase.
Identification of a new adapter protein that may link the common beta subunit of the receptor for granulocyte/macrophage colony-stimulating factor, interleukin (IL)-3, and IL-5 to phosphatidylinositol 3-kinase.
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鉴定出一种新的衔接蛋白，该蛋白可能将粒细胞/巨噬细胞集落刺激因子、白细胞介素 (IL)-3 和 IL-5 受体的常见 β 亚基与磷脂酰肌醇 3-激酶连接起来。
DOI：
10.1074/jbc.270.46.27817
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Feldman,RA
中科院分区：
文献类型：
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作者：
Jücker,M;Feldman,RA
人粒细胞/巨噬细胞集落刺激因子（hGM-CSF）与其受体结合后可诱导磷脂酰肌醇-3激酶（PI 3-kinase）迅速活化。由于hGM-CSF受体（hGMR）不包含与PI 3-激酶结合的共有序列，因此hGMR必须使用独特的机制来与PI 3-激酶结合并激活PI 3-激酶。在这里，我们描述了一个76-85 kDa（p80）的酪氨酸磷酸化蛋白的鉴定，该蛋白与hGMR的共同β亚基和hGM-CSF刺激的细胞中PI 3-激酶p85亚基的SH 2结构域相关。Src/Yes和林恩与p80·PI 3-激酶复合物紧密结合，表明存在于复合物中的p80和其他磷酸化酪氨酰蛋白被Src家族激酶磷酸化。p80的酪氨酸磷酸化仅在hGM-CSF或人白细胞介素-3刺激的细胞中检测到，这表明p80的激活可能对通过共同β亚基的信号传导具有特异性。我们推测p80作为一个衔接蛋白，可能参与连接hGM-CSF受体的PI 3-激酶信号通路。
Binding of human granulocyte/macrophage colony-stimulating factor (hGM-CSF) to its receptor induces the rapid activation of phosphatidylinositol-3 kinase (PI 3-kinase). As hGM-CSF receptor (hGMR) does not contain a consensus sequence for binding of PI 3-kinase, hGMR must use a distinct mechanism for its association with and activation of PI 3-kinase. Here, we describe the identification of a tyrosine-phosphorylated protein of 76-85 kDa (p80) that associates with the common β subunit of hGMR and with the SH2 domains of the p85 subunit of PI 3-kinase in hGM-CSF-stimulated cells. Src/Yes and Lyn were tightly associated with the p80•PI 3-kinase complex, suggesting that p80 and other phosphotyrosyl proteins present in the complex were phosphorylated by Src family kinases. Tyrosine phosphorylation of p80 was only detected in hGM-CSF or human interleukin-3-stimulated cells, suggesting that activation of p80 might be specific for signaling via the common β subunit. We postulate that p80 functions as an adapter protein that may participate in linking the hGM-CSF receptor to the PI 3-kinase signaling pathway.