Ruan Yuanyuan, Guo Liang, Qiao Ying, Hong Yi, Zhou Lei, Sun Linlin, Wang Lijing, Zhu Haiyan, Wang Lan, Yun Xiaojing, Xie Jianhui, Gu Jianxin
Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032, People's Republic of China.
Biochem Biophys Res Commun. 2009 Dec 11;390(2):217-22. doi: 10.1016/j.bbrc.2009.09.087. Epub 2009 Sep 26.
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.
CLEC-2是一种C型凝集素样受体，在血小板激活中起重要作用。蛇毒毒素红血细胞凝集素和内源性唾液糖蛋白血小板结合蛋白被确定为CLEC-2的配体，并在血小板激活中起刺激作用。我们之前还鉴定出了小鼠CLEC-2的两种剪接变体以及从全长形式切割下来的一个可溶性片段。然而，对于与CLEC-2细胞质区域相互作用的蛋白知之甚少。在本研究中，我们报告称活化C激酶1的受体RACK1与CLEC-2的细胞质尾部相关联。此外，RACK1的过表达通过促进其泛素-蛋白酶体降解降低了CLEC-2的稳定性，而不损害CLEC-2的表面表达和下游信号传导。综上所述，这些结果表明RACK1是CLEC-2表达的一种新型调节因子。
