ErbB4 and its isoforms -: Selective regulation of growth factor responses by naturally occurring receptor variants
ErbB4 and its isoforms -: Selective regulation of growth factor responses by naturally occurring receptor variants
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DOI：
10.1016/s1050-1738(01)00065-2
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发表时间：
2000-10-01
影响因子：
9.3
通讯作者：
Elenius, K
中科院分区：
文献类型：
--
作者：
Junttila, TT;Sundvall, M;Elenius, K
ErbB 4是表皮生长因子受体（EGFR，ErbB）家族的成员，介导对神经调节蛋白和其他EGF样生长因子的反应。ErbB 4是心血管和神经发育以及乳腺分化的中心调节因子。ErbB 4的作用也与恶性肿瘤和心脏病有关。最近已经鉴定出四种结构和功能不同的ErbB 4同种型。一对亚型在其细胞外质膜结构域内不同。这些跨膜ErbB 4同种型对释放可溶性受体胞外域的蛋白水解加工敏感或具有抗性。另一对ErbB 4亚型在其胞质尾区中不同。细胞内信号转导途径的分析表明，两种胞质ErbB 4亚型都可以与Shc-MAPK信号途径偶联，而另一种则无法与磷酸肌醇3-激酶（PI 3-K）-Akt信号途径偶联。信号级联激活的差异反映在通过细胞质同种型刺激的细胞反应中。两种胞质ErbB 4亚型都能刺激增殖，但不能激活PI 3-K的亚型在刺激细胞存活和趋化性方面有缺陷。这四种天然存在的受体变体一起为控制生长因子刺激的细胞反应提供了新的多样性水平。因此，ErbB 4亚型可能在各种发育和病理过程的调节中具有独特和特定的作用。（Trends Medium 10;2000：304-310）。(C)2001年，Elsevier Science Inc.
ErbB4 is a member of the epidermal growth factor receptor (EGFR, ErbB) family that mediates responses to neuregulins and other EGF-like growth factors. ErbB4 is a central regulator of cardiovascular and neural development as well as differentiation of the mammary gland. A role for ErbB4 has also been implicated in malignancies and heart diseases. Four structurally and functionally distinct ErbB4 isoforms have recently been identified. One pair of isoforms differs within their extracellular juxtamembrane domains. These juxtamembrane ErbB4 isoforms are either susceptible or resistant to proteolytic processing that release a soluble receptor ectodomain. Another pair of ErbB4 isoforms differs within their cytoplasmic tails. Analysis of the intracellular signal transduction pathways indicates that both cytoplasmic ErbB4 isoforms can couple to the Shc-MAPK signaling pathway, while the other one is incapable of coupling to the phosphoinositide 3-kinase (PI3-K)-Akt pathway. The differences in the activation of signaling cascades are reflected in the cellular responses stimulated via the cytoplasmic isoforms. Both cytoplasmic ErbB4 isoforms can stimulate proliferation, but the isoform that cannot activate PI3-K is defective in stimulating cellular survival and chemotaxis. Together these four naturally occurring receptor variants provide a new level of diversity to the control of growth factor-stimulated cellular responses. Thus, the ErbB4 isoforms may have distinct and specific roles in the regulation of various developmental and pathological processes. (Trends Cardiovasc Med 10;2000:304-310). (C) 2001, Elsevier Science Inc.