PECAM-1 functions as a negative regulator of laminin-induced platelet activation. J Thromb Haemost 2010 Jul;8(7):1584-93
Date
04/21/2010Pubmed ID
20403098Pubmed Central ID
PMC2909358DOI
10.1111/j.1538-7836.2010.03883.xScopus ID
2-s2.0-77955032687 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
SUMMARY BACKGROUND: Interaction of resting platelets with exposed components of the subendothelial matrix is an important early activating event that takes place at sites of vascular injury. Platelet responses to collagen are mediated by integrin alpha(2)beta(1) and the glycoprotein (GP)VI-Fc receptor (FcR) gamma-chain complex, whereas platelet activation by laminin is mediated by the related integrin, alpha(6)beta(1), and similarly requires signaling through GPVI-FcR gamma-chain.
OBJECTIVE: Because the cell adhesion and signaling receptor PECAM-1 has previously been shown to dampen collagen-induced platelet activation, we sought to determine whether PECAM-1 might similarly regulate platelet activation by laminin.
METHODS/RESULTS: We found that PECAM-1 became tyrosine phosphorylated on its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs following adhesion of either human or murine platelets to immobilized laminin. Whereas the presence or absence of PECAM-1 had no effect on either the rate or extent of platelet adhesion or spreading on laminin, PECAM-1 inhibited laminin-induced phosphorylation of GPVI-FcR gamma-chain immunoreceptor tyrosine-based activation motifs (ITAMs) and activation of its downstream effector, Syk kinase, and suppressed granule secretion.
CONCLUSIONS: Taken together, these data are consistent with previous findings in platelets and other blood and vascular cells that PECAM-1 functions by modulating ITAM-mediated signaling pathways that amplify cellular activation.
Author List
Crockett J, Newman DK, Newman PJAuthors
Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of WisconsinDebra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsHumans
Kinetics
Laminin
Mice
Phosphorylation
Platelet Activation
Platelet Adhesiveness
Platelet Endothelial Cell Adhesion Molecule-1
Platelet Membrane Glycoproteins
Receptors, IgG