ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling
ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling
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DOI：
10.1093/emboj/16.7.1647
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发表时间：
1997-04-01
期刊：
影响因子：
11.4
通讯作者：
Hynes, NE
中科院分区：
文献类型：
--
作者：
GrausPorta, D;Beerli, RR;Hynes, NE
我们分析了表皮生长因子（EGF）相关肽在自然表达四种ErbB受体的细胞系中诱导的ErbB受体相互作用，通过细胞内特异性抗体表达下调细胞表面ErbB-1或ErbB-2，使我们能够描述这些受体在以下信号传导过程中的作用：EGF和肝素结合的EGF (HB-EGF)， ErbB-1配体；β细胞素（ETC）， ErbB-1和ErbB-4的配体；和新分化因子（NDF）， ErbB-3和ErbB-4的配体，配体诱导的ErbB受体异二聚化遵循严格的等级，ErbB-2是所有ErbB蛋白的首选异二聚化伙伴，NDF激活的ErbB-3或ErbB-4仅在没有ErbB-2时与ErbB-1异二聚化，如果所有ErbB受体存在，NDF受体优先与ErbB-2二聚化，此外，EGF和etc诱导的ErbB-3激活在缺乏ErbB-2时受损。最后，ErbB-1被所有EGF相关肽（EGF、HB-EGF、ETC和NDF）激活与SHC偶联，而只有ErbB-1被自身配体激活与Cbl结合并磷酸化。这些结果提供了第一个生化证据，表明给定的ErbB受体具有不同的信号特性，这取决于其二聚体。
We have analyzed ErbB receptor interplay induced by the epidermal growth factor (EGF)-related peptides in cell lines naturally expressing the four :ErbB receptors, Down-regulation of cell surface ErbB-1 or ErbB-2 by intracellular expression of specific antibodies has allowed us to delineate the role of these receptors during signaling elicited by: EGF and heparin binding EGF (HB-EGF), ligands of ErbB-1; betacellulin (ETC), a ligand of ErbB-1 and ErbB-4; and neu differentiation factor (NDF), a ligand of ErbB-3 and ErbB-4, Ligand-induced ErbB receptor heterodimerization follows a strict hierarchy and ErbB-2 is the preferred heterodimerization partner of all ErbB proteins, NDF-activated ErbB-3 or ErbB-4 heterodimerize with ErbB-1 only when no ErbB-2 is available, If ail ErbB receptors are present, NDF receptors preferentially dimerize with ErbB-2, Furthermore, EGF- and ETC-induced activation of ErbB-3 is impaired in the absence of ErbB-2, suggesting that ErbB-2 has a role in the lateral transmission of signals between other ErbB receptors, Finally, ErbB-1 activated by all EGF-related peptides (EGF, HB-EGF, ETC and NDF) couples to SHC, whereas only ErbB-1 activated by fits own ligands associates with and phosphorylates Cbl, These results provide the first biochemical evidence that a given ErbB receptor has distinct signaling properties depending on its dimerization.