细胞对神经调节蛋白的反应受erbB受体家族复杂相互作用的调控。
The cellular response to neuregulins is governed by complex interactions of the erbB receptor family.
作者信息
Riese D J, van Raaij T M, Plowman G D, Andrews G C, Stern D F
机构信息
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520-8023, USA.
出版信息
Mol Cell Biol. 1995 Oct;15(10):5770-6. doi: 10.1128/MCB.15.10.5770.
Abstract
Deregulated signaling by the four members of the epidermal growth factor receptor tyrosine kinase family (erbB family) is implicated in the genesis or progression of human cancers. However, efforts to analyze signaling by these receptors have been hampered by the diversity of ligands and extensive interreceptor cross talk. We have expressed the four human erbB family receptors, singly and in pairwise combinations, in a pro-B-lymphocyte cell line (Ba/F3) and investigated the range of interactions activated by the epidermal growth factor homology domain of the agonist neuregulin beta. The results provide the first comprehensive analysis of the response of this receptor family to a single peptide agonist. This peptide induced complex patterns of receptor tyrosine phosphorylation and regulation of Ba/F3 cell survival and proliferation. These data demonstrate the existence of several previously undocumented receptor interactions driven by neuregulin.
摘要
表皮生长因子受体酪氨酸激酶家族（erbB家族）的四名成员的信号传导失调与人类癌症的发生或进展有关。然而，这些受体的信号传导分析工作受到配体多样性和广泛的受体间串扰的阻碍。我们已在原B淋巴细胞系（Ba/F3）中单独及成对表达了四种人类erbB家族受体，并研究了激动剂神经调节蛋白β的表皮生长因子同源结构域激活的相互作用范围。这些结果首次全面分析了该受体家族对单一肽激动剂的反应。这种肽诱导了复杂的受体酪氨酸磷酸化模式以及对Ba/F3细胞存活和增殖的调节。这些数据证明了由神经调节蛋白驱动的几种先前未记录的受体相互作用的存在。
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Efficient coupling with phosphatidylinositol 3-kinase, but not phospholipase C gamma or GTPase-activating protein, distinguishes ErbB-3 signaling from that of other ErbB/EGFR family members.与磷脂酰肌醇3激酶的有效偶联，而非磷脂酶Cγ或GTP酶激活蛋白，使ErbB - 3信号传导有别于其他ErbB/表皮生长因子受体（EGFR）家族成员的信号传导。
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