RACK1 associates with CLEC-2 and promotes its ubiquitin-proteasome degradation

Clec-2 is a c-type lectin-like receptor and plays an important role in platelet activation. snake venom toxin rhodocytin and the endogenous sialoglycoprotein podoplanin are identified as ligands for clec-2 and function as stimulators in platelet activation. we also previously indentified two splice variants of murine clec-2 as well as a soluble fragment cleaved from the full-length form. however, little is known about the interacting partners with the cytoplasmic region of clec-2. in this study, we reported that rack1, the receptor for activated c-kinase 1, associated with the cytoplasmic tail of clec-2. moreover, overexpression of rack 1 decreased the stability of clec-2 through promoting its ubiquitin-proteasome degradation, without impairing surface expression and downstream signaling of clec-2. taken together, these results suggest rack1 as a novel modulator of clec-2 expression. (c) 2009 elsevier inc. all rights reserved.