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 RACK1 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.
Ruan
Yuanyuan
Y
Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032, People's Republic of China.
Guo
Liang
L
Qiao
Ying
Y
Hong
Yi
Y
Zhou
Lei
L
Sun
Linlin
L
Wang
Lijing
L
Zhu
Haiyan
H
Wang
Lan
L
Yun
Xiaojing
X
Xie
Jianhui
J
Gu
Jianxin
J
D017398:Alternative Splicing; D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D055550:Protein Stability; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism*
C104778:CLEC2B protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D019204:GTP-Binding Proteins