RACK1 associates with CLEC-2 and promotes its ubiquitin-proteasome degradation.
RACK1 associates with CLEC-2 and promotes its ubiquitin-proteasome degradation.
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DOI：
10.1016/j.bbrc.2009.09.087
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发表时间：
2009-12
影响因子：
3.1
通讯作者：
Yuanyuan Ruan;Liang Guo;Y. Qiao;Yi Hong;Lei Zhou;Lin-lin Sun;Lijing Wang;Haiyan Zhu;Lan Wang;Xiao-jing Yun;Jianhui Xie;J. Gu
中科院分区：
文献类型：
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作者：
Yuanyuan Ruan;Liang Guo;Y. Qiao;Yi Hong;Lei Zhou;Lin-lin Sun;Lijing Wang;Haiyan Zhu;Lan Wang;Xiao-jing Yun;Jianhui Xie;J. Gu
CLEC-2是一种C型凝集素样受体，在血小板活化中发挥重要作用。蛇毒毒素罗多菌素和内源性唾液酸糖蛋白泊多拉宁被确定为CLEC-2的配体，并在血小板激活中发挥刺激作用。我们还鉴定了小鼠CLEC-2的两个剪接变体以及从全长形式切割的可溶片段。然而，对于与CLEC-2细胞质区域相互作用的伙伴却知之甚少。在这项研究中，我们报道了活化的C-激酶1的受体RACK1与CLEC-2的细胞质尾巴相关。此外，RACK1的过表达通过促进泛素-蛋白酶体的降解降低了CLEC-2的稳定性，而不影响CLEC-2的表面表达和下游信号转导。综上所述，这些结果表明RACK1是一种新的CLEC-2表达调节剂。
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.