Plasmin-induced migration requires signaling through protease-activated receptor 1 and integrin alpha(9)beta(1).
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.
Majumdar
Mousumi
M
Department of Dermatology, University of California Davis Medical Center, Sacramento, California 95817, USA.
Tarui
Takehiko
T
Shi
Biao
B
Akakura
Nobuaki
N
Ruf
Wolfram
W
Takada
Yoshikazu
Y
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*
D016023:Integrins; D044463:Receptor, PAR-1; C113256:integrin alpha 9 beta 1; D005341:Fibrinolysin