受体酪氨酸激酶
神经调节蛋白
ErbB公司
外域
原肌球蛋白受体激酶C
酪氨酸激酶
化学
细胞生物学
ROR1型
血小板源性生长因子受体
ERBB4公司
原癌基因酪氨酸蛋白激酶Src
磷酸化
信号转导
生物
生物化学
受体
生长因子
作者
Chang-Yuan Ni,M. Paul Murphy,Todd E. Golde,Graham Carpenter
出处
期刊:Science
[American Association for the Advancement of Science]
日期:2001-12-07
卷期号:294 (5549): 2179-2181
被引量:848
标识
DOI:10.1126/science.1065412
摘要
ErbB-4 is a transmembrane receptor tyrosine kinase that regulates cell proliferation and differentiation. After binding of its ligand heregulin (HRG) or activation of protein kinase C (PKC) by 12- O -tetradecanoylphorbol-13-acetate (TPA), the ErbB-4 ectodomain is cleaved by a metalloprotease. We now report a subsequent cleavage by γ-secretase that releases the ErbB-4 intracellular domain from the membrane and facilitates its translocation to the nucleus. γ-Secretase cleavage was prevented by chemical inhibitors or a dominant negative presenilin. Inhibition of γ-secretase also prevented growth inhibition by HRG. γ-Secretase cleavage of ErbB-4 may represent another mechanism for receptor tyrosine kinase–mediated signaling.
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