The ADAM (adisintegrin and metalloprotease) family of proteins possess both proteolytic and adhesive domains. We have established previously that the disintegrin domain of ADAM28, an ADAM expressed by human lymphocytes, is recognized by the integrin α4β1. The present study characterizes the integrin binding properties of the disintegrin-like domains of human ADAM7, ADAM28 and ADAM33 with the integrins α4β1, α4β7 and α9β1. Cell-adhesion assays demonstrated that, similar to ADAM28, the ADAM7 disintegrin domain supported α4β1-dependent Jurkat cell adhesion, whereas the ADAM33 disintegrin domain did not. The lymphocyte integrin α4β7 was also found to recognize both disintegrin domains of ADAM7 and ADAM28, but not of ADAM33. This is the first demonstration that mammalian disintegrins are capable of interacting with α4β7. All three disintegrin domains supported α9β1-dependent cell adhesion. Recognition by both α4β1 and α4β7 of ADAM7 and ADAM28 was activation-dependent, requiring either the presence of Mn2+ or an activating monoclonal antibody for cell attachment. Charge-to-alanine mutagenesis experiments revealed that the same residues within an individual ADAM disintegrin domain function in recognizing multiple integrins. However, the residues within a specific region of each ADAM disintegrin-like domain required for integrin binding were distinct. These results establish that ADAM7 and ADAM28 are recognized by the leucocyte integrins α4β1, α4β7 and α9β1. ADAM33 exclusively supported only α9β1-dependent adhesion.
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Research Article|
March 22 2005
ADAM disintegrin-like domain recognition by the lymphocyte integrins α4β1 and α4β7
Lance C. BRIDGES;
Lance C. BRIDGES
1
*Department of Biochemistry and Molecular Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, U.S.A.
1To whom correspondence should be addressed, at Department of Cell Biology, UVA Health System, School of Medicine, P.O. Box 800732, Charlottesville, VA 22908-0732, U.S.A. (email lcb5a@virginia.edu).
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Dean SHEPPARD;
Dean SHEPPARD
†Lung Biology Center and Department of Medicine, University of California, San Francisco, CA 94143, U.S.A.
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Ron D. BOWDITCH
Ron D. BOWDITCH
*Department of Biochemistry and Molecular Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, U.S.A.
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Publisher: Portland Press Ltd
Received:
August 24 2004
Revision Received:
October 11 2004
Accepted:
October 26 2004
Accepted Manuscript online:
October 26 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 387 (1): 101–108.
Article history
Received:
August 24 2004
Revision Received:
October 11 2004
Accepted:
October 26 2004
Accepted Manuscript online:
October 26 2004
Citation
Lance C. BRIDGES, Dean SHEPPARD, Ron D. BOWDITCH; ADAM disintegrin-like domain recognition by the lymphocyte integrins α4β1 and α4β7. Biochem J 1 April 2005; 387 (1): 101–108. doi: https://doi.org/10.1042/BJ20041444
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