Shedding light on sheddases: role in growth and development
Shedding light on sheddases: role in growth and development
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DOI：
10.1002/bies.10037
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发表时间：
2002-01-01
期刊：
影响因子：
4
通讯作者：
Werb, Z
中科院分区：
文献类型：
--
作者：
Kheradmand, F;Werb, Z
几种整合膜蛋白的胞外结构域通过称为“胞外结构域脱落”的过程由称为“脱落酶”的一组酶从细胞表面释放。由于许多跨膜生长和分化因子，包括在发育中起关键作用的表皮生长因子（EGF）家族的成员，需要胞外域脱落以在体内发挥适当作用，因此蛋白水解现在被视为发育胚胎中的调节机制。Zhao等人最近的两份报告提供了ADAM（一种去整合素和金属蛋白酶）在小鼠肺发育中细胞表面蛋白水解作用的证据。((1（2））通过基于异羟肟酸的金属蛋白酶抑制剂（TAPI）抑制肿瘤坏死因子-α转化酶（TACE，ADAM 17），（（1））或TACE的Zn 2+结合结构域中的靶向突变，（（2））破坏肺发育中的两种基本上皮功能：分支形态发生和细胞分化。亚当斯作为脱落酶在发育和生长因子信号传导中的作用的证据进行了讨论。(C)2002年John Wiley Sons，Inc.
The extracellular domains of several integral membrane proteins are released from the cell surface by a group of enzymes known as "sheddases" through a process called "ectodomain shedding". Because many transmembrane growth and differentiation factors, including members of the epidermal growth factor (EGF) family that play a crucial role in development, require ectodomain shedding for proper action in vivo, proteolysis is now viewed as a regulatory mechanism in the developing embryos. Two recent reports by Zhao et al. provide evidence for the role of cell surface proteolysis by an ADAM (a disintegrin and metalloprotease) in the development of murine lung.((1,2)) Inhibition of tumor necrosis factor-a converting enzyme (TACE, ADAM17) by the hydroxamic acid-based metalloprotease inhibitor (TAPI),((1)) or a targeted mutation in Zn2+-binding domain of TACE,((2)) disrupts two essential epithelial functions in lung development: branching morphogenesis and cytodifferentiation. Evidence for the role of ADAMs as sheddases in development and growth factor signaling is discussed. (C) 2002 John Wiley Sons, Inc.