title: Interaction of the disintegrin and cysteine-rich domains of ADAM12 with integrin alpha7beta1.
abstract: We describe a novel interaction between the disintegrin and cysteine-rich (DC) domains of ADAM12 and the integrin alpha7beta1. Integrin alpha7beta1 extracted from human embryonic kidney 293 cells transfected with alpha7 cDNA was retained on an affinity column containing immobilized DC domain of ADAM12. 293 cells stably transfected with alpha7 cDNA adhered to DC-coated wells, and this adhesion was partially inhibited by 6A11 integrin alpha7 function-blocking antibody. The X1 and the X2 extracellular splice variants of integrin alpha7 supported equally well adhesion to the DC protein. Integrin alpha7beta1-mediated cell adhesion to DC had different requirements for Mn2+ than adhesion to laminin. Furthermore, integrin alpha7beta1-mediated cell adhesion to laminin, but not to DC, resulted in efficient cell spreading and phosphorylation of focal adhesion kinase (FAK) at Tyr397. We also show that adhesion of L6 myoblasts to DC is mediated in part by the endogenous integrin alpha7beta1 expressed in these cells. Since integrin alpha7 plays an important role in muscle cell growth, stability, and survival, and since ADAM12 has been implicated in muscle development and regeneration, we postulate that the interaction between ADAM12 and integrin alpha7beta1 may be relevant to muscle development, function, and disease. We also conclude that laminin and the DC domain of ADAM12 represent two functional ligands for integrin alpha7beta1, and adhesion to each of these two ligands via integrin alpha7beta1 triggers different cellular responses.
authors.affiliation: Department of Biochemistry, Kansas State University, Manhattan 66506, USA.
authors.forename: Zhefeng
authors.initials: Z
authors.lastname: Zhao
authors.forename: Joanna
authors.initials: J
authors.lastname: Gruszczynska-Biegala
authors.forename: Tracey
authors.initials: T
authors.lastname: Cheuvront
authors.forename: Haiqing
authors.initials: H
authors.lastname: Yi
authors.forename: Helga
authors.initials: H
authors.lastname: von der Mark
authors.forename: Klaus
authors.initials: K
authors.lastname: von der Mark
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kaufman
authors.forename: Anna
authors.initials: A
authors.lastname: Zolkiewska
mesh_terms: D051722:ADAM Proteins; D000072199:ADAM12 Protein; D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism; D019483:Disintegrins / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008024:Ligands; D008345:Manganese / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D032446:Myoblasts / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
chemical_list: D019483:Disintegrins; D016023:Integrins; D007797:Laminin; D008024:Ligands; D008565:Membrane Proteins; D014443:Tyrosine; D008345:Manganese; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496052:Ptk2 protein, rat; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; D008666:Metalloendopeptidases; D003545:Cysteine; C082908:integrin alpha7beta1