title: Plasmin-induced migration requires signaling through protease-activated receptor 1 and integrin alpha(9)beta(1).
abstract: Plasmin is a major extracellular protease that elicits intracellular signals to mediate platelet aggregation, chemotaxis of peripheral blood monocytes, and release of arachidonate and leukotriene from several cell types in a G protein-dependent manner. Angiostatin, a fragment of plasmin(ogen), is a ligand and an antagonist for integrin alpha(9)beta(1). Here we report that plasmin specifically interacts with alpha(9)beta(1) and that plasmin induces of cells expressing migration recombinant alpha(9)beta(1) (alpha(9)-Chinese hamster ovary (CHO) cells). Migration was dependent on an interaction of the kringle domains of plasmin with alpha(9)beta(1) as well as the catalytic activity of plasmin. Angiostatin, representing the kringle domains of plasmin, alone did not induce the migration of alpha(9)-CHO cells, but simultaneous activation of the G protein-coupled protease-activated receptor (PAR)-1 with an agonist peptide induced the migration on angiostatin, whereas PAR-2 or PAR-4 agonist peptides were without effect. Furthermore, a small chemical inhibitor of PAR-1 (RWJ 58259) and a palmitoylated PAR-1-blocking peptide inhibited plasmin-induced migration of alpha(9)-CHO cells. These results suggest that plasmin induces migration by kringle-mediated binding to alpha(9)beta(1) and simultaneous proteolytic activation of PAR-1.
authors.affiliation: Department of Dermatology, University of California Davis Medical Center, Sacramento, California 95817, USA.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Majumdar
authors.forename: Takehiko
authors.initials: T
authors.lastname: Tarui
authors.forename: Biao
authors.initials: B
authors.lastname: Shi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Akakura
authors.forename: Wolfram
authors.initials: W
authors.lastname: Ruf
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Takada
mesh_terms: D000818:Animals; D016466:CHO Cells; D002384:Catalysis; D002465:Cell Movement / Q000502:physiology*; D006224:Cricetinae; D005341:Fibrinolysin / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D011485:Protein Binding; D044463:Receptor, PAR-1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016023:Integrins; D044463:Receptor, PAR-1; C113256:integrin alpha 9 beta 1; D005341:Fibrinolysin