Outside-in signals delivered by matrix metalloproteinase-1 regulate platelet function
| Autor: | Spencer W. Galt, Thomas M. McIntyre, Andrew S. Weyrich, Jeanne M. Falk, Stephen M. Prescott, Donald J. Medd, Stephan Lindemann, Loren L. Allen, Larry W. Kraiss, Guy A. Zimmerman |
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| Rok vydání: | 2002 |
| Předmět: |
Blood Platelets
Platelet Aggregation Physiology Integrin Platelet Membrane Glycoproteins Biology Matrix metalloproteinase Matrix Metalloproteinase Inhibitors Extracellular matrix Antigens CD Humans Protease Inhibitors Platelet activation Phosphorylation Metalloproteinase Proteolytic enzymes Integrin beta3 Proteins Platelet Activation Cell biology Biochemistry biology.protein Signal transduction Matrix Metalloproteinase 1 Cardiology and Cardiovascular Medicine Intracellular Signal Transduction |
| Zdroj: | Circulation research. 90(10) |
| ISSN: | 1524-4571 |
| Popis: | Abstract — Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade extracellular matrix proteins. These enzymes are implicated in a variety of physiological and pathological events characterized by extracellular matrix remodeling. Recent studies suggest that MMPs may have a signaling capacity, but direct evidence supporting this concept is lacking. In the present study, we demonstrate that outside-in signals delivered by exogenous MMP-1 (interstitial collagenase) markedly increase the number of tyrosine-phosphorylated proteins in platelets. Active MMP-1 also targets β 3 integrins to areas of cell contact and primes platelets for aggregation. Examination of the endogenous enzyme demonstrated that activated platelets process latent MMP-1 into its active form. Neutralization of MMP-1 activity with MMP inhibitors or specific blocking antibodies markedly attenuates agonist-induced phosphorylation of intracellular proteins, movement of β 3 integrins to cell contact points, and intercellular aggregation. The finding that MMP-1 is rapidly activated in platelets and controls functional responses identifies a new role for this metalloproteinase as a signaling molecule that regulates thrombotic events. |
| Databáze: | OpenAIRE |
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