Potential role of kringle-integrin interaction in plasmin and uPA actions (A hypothesis)

Yoshikazu Takada

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We previously showed that the kringle domains of plasmin and angiostatin, the N-terminal four kringles (K14) of plasminogen, directly bind to integrins. Angiostatin blocks tumor-mediated angiogenesis and has great therapeutic potential. Angiostatin binding to integrins may be related to the antiinflammatory action of angiostatin. We reported that plasmin induces signals through protease-activated receptor (PAR-1), and plasmin-integrin interaction may be required for enhancing plasmin concentration on the cell surface, and enhances its signaling function. Angiostatin binding to integrin does not seem to induce proliferative signals. One possible mechanism of angiostatin's inhibitory action is that angiostatin suppresses plasmin-induced PAR-1 activation by competing with plasmin for binding to integrins. Interestingly, plasminogen did not interact with α v β 3, suggesting that the α v β 3 -binding sites in the kringle domains of plasminogen are cryptic. The kringle domain of urokinase-type plasminogen activator (uPA) also binds to integrins. The uPA-integrin interaction enhances uPA concentrations on the cell surface and enhances plasminogen activation on the cell surface. It is likely that integrins bind to the kringle domain, and uPAR binds to the growth factor-like domain (GFD) of uPA simultaneously, making the uPAR-uPA-integrin ternary complex. We present a docking model of the ternary complex.

Original languageEnglish
Article number136302
JournalJournal of Biomedicine and Biotechnology
Volume2012
DOIs
Publication statusPublished - 2012
Externally publishedYes

Fingerprint

Kringles
Angiostatins
Fibrinolysin
Urokinase-Type Plasminogen Activator
Integrins
Plasminogen
Chemical activation
Proteinase-Activated Receptors
PAR-1 Receptor
Tumors
Intercellular Signaling Peptides and Proteins
Anti-Inflammatory Agents
Binding Sites

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Genetics
  • Molecular Biology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

Cite this

Potential role of kringle-integrin interaction in plasmin and uPA actions (A hypothesis). / Takada, Yoshikazu.

In: Journal of Biomedicine and Biotechnology, Vol. 2012, 136302, 2012.

Research output: Contribution to journalArticle

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