Syk and Src Family Kinases Regulate C-type Lectin Receptor 2 (CLEC-2)-mediated Clustering of Podoplanin and Platelet Adhesion to Lymphatic Endothelial Cells

Abstract

Background: The interaction of platelet CLEC-2 with Podoplanin is critical for development of the lymphatics.Results: CLEC-2 forms a central cluster upon engagement with Podoplanin, which clusters Podoplanin. Clustering is dependent on Syk and is critical for adhesion.Conclusion: Clustering regulates the interaction of platelets with lymphatic endothelial cells.Significance: These findings account for the similar lymphatic phenotype of CLEC-2- and Syk-deficient mice.

Modulation of VEGF-induced migration and network formation by lymphatic endothelial cells: Roles of platelets and podoplanin

“…Migration of LEC was also suppressed when murine platelets were added, but the effect was significantly reduced when the platelets were derived from mice lacking expression of CLEC-2. Taken together, the results strongly suggest that the effects of platelets were mediated through crosslinking of podoplanin by CLEC-2, which has previously been shown to be able to fulfill that function [12,39].…”

New Insights into the Role of Podoplanin in Epithelial–Mesenchymal Transition

“…There are two clear functions described for podoplanin; one is its role in immune cells interactions (Acton et al, 2014;Astarita et al, 2014;Pollitt et al, 2014). The other is the rearrangement of the cytoskeleton and the promotion of cell motility by its interactions with ERM proteins and Rho GTPases.…”

Anti–miR-148a regulates platelet FcγRIIA signaling and decreases thrombosis in vivo in mice

“…54-56 CLEC-2, another tyrosine kinase pathway receptor containing hemITAM on platelets, is important in separation of the vascular system and lymphatic system [57][58][59] and thrombotic stability. 60 Neither TULA-2 nor miR-148a was indicated to affect CLEC-2 signaling by previous studies.…”