PECAM-1 functions as a negative regulator of laminin-induced platelet activation.
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.


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.
Crockett
J
J
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 5320, USA.
Newman
D K
DK
Newman
P J
PJ
D000818:Animals; D006801:Humans; D007700:Kinetics; D007797:Laminin / Q000494:pharmacology*; D051379:Mice; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism
D007797:Laminin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010980:Platelet Membrane Glycoproteins; D017452:Receptors, IgG; C098341:platelet membrane glycoprotein VI
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