title: ADAM disintegrin-like domain recognition by the lymphocyte integrins alpha4beta1 and alpha4beta7.
abstract: The ADAM (a disintegrin 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 alpha4beta1. The present study characterizes the integrin binding properties of the disintegrin-like domains of human ADAM7, ADAM28 and ADAM33 with the integrins alpha4beta1, alpha4beta7 and alpha9beta1. Cell-adhesion assays demonstrated that, similar to ADAM28, the ADAM7 disintegrin domain supported alpha4beta1-dependent Jurkat cell adhesion, whereas the ADAM33 disintegrin domain did not. The lymphocyte integrin alpha4beta7 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 alpha4beta7. All three disintegrin domains supported alpha9beta1-dependent cell adhesion. Recognition by both alpha4beta1 and alpha4beta7 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 alpha4beta1, alpha4beta7 and alpha9beta1. ADAM33 exclusively supported only alpha9beta1-dependent adhesion.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA. lcb5a@virginia.edu
authors.forename: Lance C
authors.initials: LC
authors.lastname: Bridges
authors.forename: Dean
authors.initials: D
authors.lastname: Sheppard
authors.forename: Ron D
authors.initials: RD
authors.lastname: Bowditch
mesh_terms: D051722:ADAM Proteins; D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D019169:Jurkat Cells / Q000737:chemistry / Q000378:metabolism; D020014:K562 Cells / Q000737:chemistry / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D039041:Integrin alpha4beta1; D016023:Integrins; D008562:Membrane Glycoproteins; D010455:Peptides; D016201:Receptors, Lymphocyte Homing; C113256:integrin alpha 9 beta 1; C071777:integrin alpha4beta7; D051722:ADAM Proteins; C410224:ADAM28 protein, human; C450441:ADAM33 protein, human; C438783:ADAM7 protein, human; D008666:Metalloendopeptidases