Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland.
PLoS One. 2015 Mar 31;10(3):e0121301. doi: 10.1371/journal.pone.0121301. eCollection 2015.
A disintegrin and metalloproteinases (ADAMs) constitute a protein family essential for extracellular signaling and regulation of cell adhesion. Catalytic activity of ADAMs and their predicted potential for Src-homology 3 (SH3) domain binding show a strong correlation. Here we present a comprehensive characterization of SH3 binding capacity and preferences of the catalytically active ADAMs 8, 9, 10, 12, 15, 17, and 19. Our results revealed several novel interactions, and also confirmed many previously reported ones. Many of the identified SH3 interaction partners were shared by several ADAMs, whereas some were ADAM-specific. Most of the ADAM-interacting SH3 proteins were adapter proteins or kinases, typically associated with sorting and endocytosis. Novel SH3 interactions revealed in this study include TOCA1 and CIP4 as preferred partners of ADAM8, and RIMBP1 as a partner of ADAM19. Our results suggest that common as well as distinct mechanisms are involved in regulation and execution of ADAM signaling, and provide a useful framework for addressing the pathways that connect ADAMs to normal and aberrant cell behavior.
解整合素金属蛋白酶（ADAMs）构成了一个对细胞外信号转导和细胞黏附调控至关重要的蛋白质家族。ADAMs 的催化活性及其潜在的Src 同源结构域 3（SH3）结合预测显示出很强的相关性。在这里，我们全面描述了催化活性的 ADAMs8、9、10、12、15、17 和 19 的 SH3 结合能力和偏好。我们的结果揭示了一些新的相互作用，同时也证实了许多先前报道的相互作用。许多鉴定出的 ADAM 与 SH3 的相互作用伙伴被多个 ADAMs 共享，而有些则是 ADAM 特异性的。大多数与 ADAM 相互作用的 SH3 蛋白是衔接蛋白或激酶，通常与分拣和内吞作用有关。在这项研究中揭示的新的 SH3 相互作用包括 TOCA1 和 CIP4 是 ADAM8 的首选伙伴，而 RIMBP1 是 ADAM19 的伙伴。我们的结果表明，共同的和独特的机制都参与了 ADAM 信号的调节和执行，并为解决 ADAMs 与正常和异常细胞行为之间的通路提供了一个有用的框架。
