MDC-9 (ADAM-9/Meltrin gamma) functions as an adhesion molecule by binding the alpha(v)beta(5) integrin.
MDC-9 is a widely expressed member of the metalloproteinase/disintegrin/cysteine-rich protein family. The disintegrin domain of MDC-9 lacks an RGD motif but has recently been reported to bind the alpha(6)beta(1) integrin; however, it is unclear whether MDC-9 can bind other integrins. In the present study myeloma cells, but not lymphoblastoid cells, were shown to bind to immobilised, recombinantly expressed MDC-9 disintegrin domain (A9dis). Binding was divalent cation-dependent, being supported by Mn(2+) and Ca(2+). Adhesion of myeloma cells to A9dis was completely inhibited by an antibody to the alpha(v)beta(5) integrin but not by antibodies to other subunits. RGD-containing peptides had no effect on binding, suggesting that MDC-9 interacts with alpha(v)beta(5) in an RGD-independent manner. Flow cytometric analyses demonstrated that myeloma cells, but not lymphoblastoid cells, expressed alpha(v)beta(5) on the cell membrane. These data indicated that the disintegrin domain of MDC-9 can function as an adhesion molecule by interacting with an alpha(v)beta(5) integrin.
Zhou
M
M
Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, United Kingdom.
Graham
R
R
Russell
G
G
Croucher
P I
PI
D051722:ADAM Proteins; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019483:Disintegrins / Q000737:chemistry; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000378:metabolism*; D008223:Lymphoma / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases; D009101:Multiple Myeloma / Q000737:chemistry / Q000378:metabolism; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D019030:Receptors, Vitronectin; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D019483:Disintegrins; D016023:Integrins; D008565:Membrane Proteins; D009124:Muscle Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D019030:Receptors, Vitronectin; D011993:Recombinant Fusion Proteins; C064660:integrin alphaVbeta5; C047981:arginyl-glycyl-aspartic acid; D051722:ADAM Proteins; C098339:ADAM9 protein, human; D008666:Metalloendopeptidases