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Multiple non-catalytic ADAMs are novel integrin α4 ligands

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Abstract

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.

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Acknowledgements

This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health and internal funds from the Arkansas College of Osteopathic Medicine and Brody School of Medicine at East Carolina University.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, The Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA

    Lei Wang, Jason A. Hoggard, Erica D. Korleski, JianMing Chen, Tonya N. Zeczycki & Lance C. Bridges

  2. Biochemistry, Molecular and Cell Sciences, Arkansas College of Osteopathic Medicine, Arkansas Colleges of Health Education, 7000 Chad Colley Blvd., Ft. Smith, AR, 72916, USA

    Gideon V. Long, Brandy C. Ree, Kenneth Hensley & Lance C. Bridges

  3. Computational and Statistical Genomics Branch, Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Stephen R. Bond & Tyra G. Wolfsberg

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  1. Lei Wang
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Wang, L., Hoggard, J.A., Korleski, E.D. et al. Multiple non-catalytic ADAMs are novel integrin α4 ligands. Mol Cell Biochem 442, 29–38 (2018). https://doi.org/10.1007/s11010-017-3190-y

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