Phosphorylation-dependent binding of 14-3-3 to Par3β, a human Par3-related cell polarity protein
Phosphorylation-dependent binding of 14-3-3 to Par3β, a human Par3-related cell polarity protein
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DOI：
10.1016/j.bbrc.2005.01.115
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发表时间：
2005-04-01
影响因子：
3.1
通讯作者：
Sumimoto, H
中科院分区：
文献类型：
--
作者：
Izaki, T;Kamakura, S;Sumimoto, H
哺乳动物Par 3 α和Par 3 β/Par 3L参与细胞极性建立并定位于上皮细胞的紧密连接; Par 3 α通过结合非典型PKC（aPKC）起作用。在这里，我们表明，Par 3 β以及Par 3 α与14-3-3蛋白的磷酸化依赖的方式相互作用。在相互作用中，Par 3 β的Ser-746和Par 3 α的相应残基（Ser-814）可能起关键作用，因为这些残基被不可磷酸化的丙氨酸取代导致相互作用活性的丧失。具有替换的突变体Par 3蛋白被正确地募集到MDCK细胞的紧密连接和HeLa细胞中由小GT3 Rac的活性形式诱导的膜皱褶。因此，与14-3-3的相互作用似乎与NO定位无关。与此一致，Par 3 α-14-3-3相互作用不抑制Par 3 α定位所需的Par 3 α-aPKC结合，尽管aPKC结合位点靠近含Ser-814的14-3-3相互作用区域。(C)2005年爱思唯尔公司All rights reserved.
Mammalian Par3alpha and Par3beta/Par3L participate in cell polarity establishment and localize to tight junctions of epithelial cells; Par3alpha acts via binding to atypical PKC (aPKC). Here we show that Par3beta as well as Par3alpha interacts with 14-3-3 proteins in a phosphorylation-dependent manner. In the interaction, Ser-746 of Par3beta and the corresponding residue of Par3alpha (Ser-814) likely play a crucial role, since replacement of these residues by unphosphorylatable alanine results in a loss of interacting activity. The mutant Par3 proteins with the replacement are correctly recruited to tight junctions of MDCK cells and to membrane ruffles induced by an active form of the small GTPase Rac in HeLa cells. Thus, the interaction with 14-3-3 appears to be dispensable to NO localization. Consistent with this, the Par3alpha-14-3-3 interaction does not inhibit the Par3alpha-aPKC association required for the Par3alpha localization, although the aPKC-binding site lies close to the Ser-814-containing, 14-3-3-interacting region. (C) 2005 Elsevier Inc. All rights reserved.