The ADAM metalloproteinases.
The ADAM metalloproteinases.
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DOI：
10.1016/j.mam.2008.08.001
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发表时间：
2008-10
影响因子：
10.6
通讯作者：
Pennington CJ
中科院分区：
文献类型：
--
作者：
Edwards DR;Handsley MM;Pennington CJ
Adams（崩解蛋白和金属蛋白酶）是一个引人入胜的跨膜家族和分泌的蛋白质家族，在调节细胞表型中对细胞粘附，迁移，蛋白水解和信号传导的影响，尽管所有ADAMS都包含金属蛋白酶域，但在人类中仅13。 21家族中的基因编码功能蛋白，表明至少对于其他八个成员，蛋白质 - 蛋白质相互作用是其关键方面生物学功能。蛋白酶涉及pro-TNF-α的激活，但其Sheddase功能尤其涵盖了广泛的细胞表面分子。表皮生长因子受体（EGFR）的活性形式，其功能对于上皮组织的发展至关重要。通过Notch和Eph/Ephrin途径发出信号的主要参与者。随后的“膜内蛋白水解”（RIP）必不可少子宫。当癌症，心血管疾病，哮喘，阿尔茨海默氏病的功能失调时功能，调节和疾病参与。
The ADAMs (a disintegrin and metalloproteinase) are a fascinating family of transmembrane and secreted proteins with important roles in regulating cell phenotype via their effects on cell adhesion, migration, proteolysis and signalling. Though all ADAMs contain metalloproteinase domains, in humans only 13 of the 21 genes in the family encode functional proteases, indicating that at least for the other eight members, protein–protein interactions are critical aspects of their biological functions. The functional ADAM metalloproteinases are involved in “ectodomain shedding” of diverse growth factors, cytokines, receptors and adhesion molecules. The archetypal activity is shown by ADAM-17 (tumour necrosis factor-α convertase, TACE), which is the principal protease involved in the activation of pro-TNF-α, but whose sheddase functions cover a broad range of cell surface molecules. In particular, ADAM-17 is required for generation of the active forms of Epidermal Growth Factor Receptor (EGFR) ligands, and its function is essential for the development of epithelial tissues. Several other ADAMs have important sheddase functions in particular tissue contexts. Another major family member, ADAM-10, is a principal player in signalling via the Notch and Eph/ephrin pathways. For a growing number of substrates, foremost among them being Notch, cleavage by ADAM sheddases is essential for their subsequent “regulated intramembrane proteolysis” (RIP), which generates cleaved intracellular domains that translocate to the nucleus and regulate gene transcription. Several ADAMs play roles in spermatogenesis and sperm function, potentially by effecting maturation of sperm and their adhesion and migration in the uterus. Other non-catalytic ADAMs function in the CNS via effects on guidance mechanisms. The ADAM family are thus fundamental to many control processes in development and homeostasis, and unsurprisingly they are also linked to pathological states when their functions are dysregulated, including cancer, cardiovascular disease, asthma, Alzheimer’s disease. This review will provide an overview of current knowledge of the human ADAMs, discussing their structure, function, regulation and disease involvement.
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影响因子：
4.8
作者：
Buxbaum, JD;Liu, KN;Black, RA
通讯作者：
Black, RA
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Peiretti, Franck