Department of Biochemistry and Molecular Biology, The Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA.
Biochemistry, Molecular and Cell Sciences, Arkansas College of Osteopathic Medicine, Arkansas Colleges of Health Education, 7000 Chad Colley Blvd., Ft. Smith, AR, 72916, USA.
Mol Cell Biochem. 2018 May;442(1-2):29-38. doi: 10.1007/s11010-017-3190-y. Epub 2017 Sep 14.
The ADAM (a disintegrin and metalloprotease) protein family uniquely exhibits both catalytic and adhesive properties. In the well-defined process of ectodomain shedding, ADAMs transform latent, cell-bound substrates into soluble, biologically active derivatives to regulate a spectrum of normal and pathological processes. In contrast, the integrin ligand properties of ADAMs are not fully understood. Emerging models posit that ADAM-integrin interactions regulate shedding activity by localizing or sequestering the ADAM sheddase. Interestingly, 8 of the 21 human ADAMs are predicted to be catalytically inactive. Unlike their catalytically active counterparts, integrin recognition of these "dead" enzymes has not been largely reported. The present study delineates the integrin ligand properties of a group of non-catalytic ADAMs. Here we report that human ADAM11, ADAM23, and ADAM29 selectively support integrin α4-dependent cell adhesion. This is the first demonstration that the disintegrin-like domains of multiple catalytically inactive ADAMs are ligands for a select subset of integrin receptors that also recognize catalytically active ADAMs.
解整合素金属蛋白酶（ADAM）蛋白家族独特地表现出催化和黏附特性。在明确的细胞外结构域脱落过程中，ADAM 将潜在的、细胞结合的底物转化为可溶性的、具有生物活性的衍生物，以调节一系列正常和病理过程。相比之下，ADAM 整合素配体的特性还不完全清楚。新兴的模型假设 ADAM-整合素相互作用通过局部化或隔离 ADAM 切酶来调节脱落活性。有趣的是，21 个人类 ADAM 中的 8 个被预测为催化失活。与它们的催化活性对应物不同，这些“死”酶的整合素识别尚未得到广泛报道。本研究描述了一组非催化 ADAM 的整合素配体特性。在这里，我们报告人 ADAM11、ADAM23 和 ADAM29 选择性支持整合素 α4 依赖性细胞黏附。这是首次证明多种催化失活 ADAM 的解整合素样结构域是一组选择性整合素受体的配体，这些受体也识别催化活性 ADAM。
