Plasmin-induced migration requires signaling through protease-activated receptor 1 and integrin α9β1

Mousumi Majumdar, Takehiko Tarui, Biao Shi, Nobuaki Akakura, Wolfram Ruf, Yoshikazu Takada

Research output: Contribution to journalArticle

59 Citations (Scopus)

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 α9β1. Here we report that plasmin specifically interacts with α 9β1 and that plasmin induces migration of cells expressing recombinant α9β19-Chinese hamster ovary (CHO) cells). Migration was dependent on an interaction of the kringle domains of plasmin with α 9β1 as well as the catalytic activity of plasmin. Angiostatin, representing the kringle domains of plasmin, alone did not induce the migration of α9-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 α9-CHO cells. These results suggest that plasmin induces migration by kringle-mediated binding to α9β 1 and simultaneous proteolytic activation of PAR-1.

Original languageEnglish (US)
Pages (from-to)37528-37534
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number36
DOIs
StatePublished - Sep 3 2004

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PAR-1 Receptor
Fibrinolysin
Integrins
Angiostatins
Kringles
Cricetulus
Ovary
GTP-Binding Proteins
Peptides
Chemical activation
Cells
PAR-2 Receptor
Leukotrienes
Chemotaxis
Platelets
Platelet Aggregation
Cell Movement
Monocytes
Catalyst activity
Blood

ASJC Scopus subject areas

  • Biochemistry

Cite this

Plasmin-induced migration requires signaling through protease-activated receptor 1 and integrin α9β1 . / Majumdar, Mousumi; Tarui, Takehiko; Shi, Biao; Akakura, Nobuaki; Ruf, Wolfram; Takada, Yoshikazu.

In: Journal of Biological Chemistry, Vol. 279, No. 36, 03.09.2004, p. 37528-37534.

Research output: Contribution to journalArticle

Majumdar, Mousumi ; Tarui, Takehiko ; Shi, Biao ; Akakura, Nobuaki ; Ruf, Wolfram ; Takada, Yoshikazu. / Plasmin-induced migration requires signaling through protease-activated receptor 1 and integrin α9β1 In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 36. pp. 37528-37534.
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