The lipid raft proteins flotillins/reggies interact with Gαq and are involved in Gq-mediated p38 mitogen-activated protein kinase activation through tyrosine kinase
The lipid raft proteins flotillins/reggies interact with Gαq and are involved in Gq-mediated p38 mitogen-activated protein kinase activation through tyrosine kinase
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DOI：
10.1016/j.cellsig.2007.01.012
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发表时间：
2007-06-01
影响因子：
4.8
通讯作者：
Itoh, Hiroshi
中科院分区：
文献类型：
--
作者：
Sugawara, Yo;Nishii, Hiroko;Itoh, Hiroshi
异三聚体G蛋白α q亚基（G α q）通过激活效应分子磷脂酶Cl介导多种细胞功能。Gaq活性受G蛋白β - γ亚基、G蛋白偶联受体、RGS蛋白和ric8的调控。在本研究中，我们鉴定了脂筏驻留蛋白flotillin-1/reggie-2和flotillin-2/reggie-1为G α q结合蛋白。G α q和flotillins的相互作用不依赖于G α q的核苷酸结合状态，而flotillins的n端部分对相互作用至关重要。短时间干扰rna介导的flotillins，特别是flotillin-2的敲低，减弱了utp诱导的p38丝裂原活化蛋白激酶（MAPK）的激活，但没有减弱ERK1/2的激活。Src家族酪氨酸激酶抑制剂PP2和降胆固醇剂甲基- β -环糊精抑制p38 MAPK的激活，甲基- β -环糊精通常用于破坏脂筏。相反，ERK1/2的激活不受这些化合物的抑制。这些证据表明，Gq偶联受体通过脂筏和Src激酶激活特异性激活p38 MAPK，其中flotillins积极调节Gq信号。(c) 2007爱思唯尔公司版权所有。
The heterotrimeric G protein alpha q subunit (G alpha q) mediates a variety of cell functions by activating the effector molecule phospholipase Cl. Gaq activity is regulated by G protein beta gamma subunits, G protein-coupled receptors, RGS proteins, and Ric-8. In this study, we identified the lipid raft resident proteins, flotillin-1/reggie-2 and flotillin-2/reggie-1, as G alpha q-binding proteins. The interactions of G alpha q and flotillins were independent of the nucleotide-binding state of G alpha q, and the N-terminal portion of flotillins was critical for the interaction. A short interfering RNA-mediated knockdown of flotillins, particularly flotillin-2, attenuated the UTP-induced activation of p38 mitogen-activated protein kinase (MAPK) but not that of ERK1/2. The activation of p38 MAPK was inhibited by the Src family tyrosine kinase inhibitor PP2 and the cholesterol-depleting agent methyl-beta-cyclodextrin, which is generally used for the disruption of lipid rafts. In contrast, the activation of ERK1/2 was not inhibited by these compounds. These lines of evidence suggested that a Gq-coupled receptor activates specifically p38 MAPK through lipid rafts and Src kinase activation, in which flotillins positively modulate the Gq signaling. (c) 2007 Elsevier Inc. All rights reserved.