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Novel interactions in platelet biology: CLEC‐2/podoplanin and laminin/GPVI
Author(s) -
OZAKI Y.,
SUZUKIINOUE K.,
INOUE O.
Publication year - 2009
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2009.03372.x
Subject(s) - gpvi , podoplanin , integrin , platelet , microbiology and biotechnology , chemistry , laminin , collagen receptor , platelet activation , platelet adhesiveness , platelet glycoprotein gpib ix complex , platelet membrane glycoprotein , receptor , immunology , biology , biochemistry , extracellular matrix , immunohistochemistry , platelet aggregation
Summary. We have identified a novel platelet membrane protein, CLEC‐2 as a receptor for rhodocytin, a platelet‐activating snake venom. CLEC‐2 is specifically expressed in platelets and megakaryocytes, and has an atypical ITAM, which undergoes tyrosine phosphorylation by Src kinases, resulting in downstream signaling including Syk, SLP‐76 and PLCγ2. We found that CLEC‐2 is the receptor for podoplanin, a sialoglycoprotein implicated in tumor‐induced platelet aggregation and tumor metastasis. VWF bridges exposed collagen, at damaged vessels, to GPIb. Subsequently, GPVI binds to collagen, leading to integrin α2β1 activation. We found that platelets adhere to laminin, another major ECM component, through integrin α6β1, and are activated through GPVI. This is the first report on GPVI having a ligand, laminin, other than collagen. Laminin also interacts with VWF, leading to platelet adhesion via GPIb under sheer stress. The redundancy of platelet interactions with laminin and with collagen may serve to promote hemostasis at sites of damaged vessels.