Protein phosphatase 2A associates with and regulates atypical PKC and the epithelial tight junction complex.
Protein phosphatase 2A associates with and regulates atypical PKC and the epithelial tight junction complex.
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蛋白质磷酸酶2a与非典型PKC和上皮紧密连接络合物相关联。
DOI：
10.1083/jcb.200206114
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发表时间：
2002-09-02
期刊：
影响因子：
--
通讯作者：
Sontag E
中科院分区：
文献类型：
--
作者：
Nunbhakdi-Craig V;Machleidt T;Ogris E;Bellotto D;White CL 3rd;Sontag E
紧密连接（TJ）在上皮细胞极性的建立和细胞旁通透性的调节中起着至关重要的作用。在这里，我们表明，在钙诱导的Madin-Darby犬肾细胞的连接生物发生，ABαC，一个主要的蛋白磷酸酶（PP）2A全酶，被招募到顶端膜，在那里它与TJ复合物相互作用。增强的PP 2A活性诱导TJ蛋白、ZO-1、occludin和claudin-1的去磷酸化，并且与增加的细胞旁通透性相关。PP 2A催化亚基的表达严重阻碍了TJ组装。相反，冈田酸对PP 2A的抑制促进ZO-1、occludin和claudin-1在连接生物发生期间向TJ的磷酸化和募集。PP 2A负调控TJ组装，而不明显影响F-肌动蛋白和E-钙粘蛋白的组织。值得注意的是，抑制非典型PKC（aPKC）阻断了冈田酸诱导的TJ蛋白的钙和血清非依赖性膜再分布。事实上，PP 2A与TJ形成过程中aPKC的活性和分布相关，并对其进行重要调节。因此，我们提供了PP 2A在上皮细胞中的钙依赖性靶向的第一个证据，我们确定PP 2A作为与多蛋白TJ复合物相关的第一个丝氨酸/苏氨酸磷酸酶，我们揭示了PP 2A在调节上皮aPKC和TJ组装和功能中的新作用。
Tight junctions (TJs) play a crucial role in the establishment of cell polarity and regulation of paracellular permeability in epithelia. Here, we show that upon calcium-induced junction biogenesis in Madin-Darby canine kidney cells, ABαC, a major protein phosphatase (PP)2A holoenzyme, is recruited to the apical membrane where it interacts with the TJ complex. Enhanced PP2A activity induces dephosphorylation of the TJ proteins, ZO-1, occludin, and claudin-1, and is associated with increased paracellular permeability. Expression of PP2A catalytic subunit severely prevents TJ assembly. Conversely, inhibition of PP2A by okadaic acid promotes the phosphorylation and recruitment of ZO-1, occludin, and claudin-1 to the TJ during junctional biogenesis. PP2A negatively regulates TJ assembly without appreciably affecting the organization of F-actin and E-cadherin. Significantly, inhibition of atypical PKC (aPKC) blocks the calcium- and serum-independent membrane redistribution of TJ proteins induced by okadaic acid. Indeed, PP2A associates with and critically regulates the activity and distribution of aPKC during TJ formation. Thus, we provide the first evidence for calcium-dependent targeting of PP2A in epithelial cells, we identify PP2A as the first serine/threonine phosphatase associated with the multiprotein TJ complex, and we unveil a novel role for PP2A in the regulation of epithelial aPKC and TJ assembly and function.
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三个紧密连接相关的Maguks ZO-1，ZO-2和ZO-3与Claudins的Cooh Termini直接结合。
DOI：
10.1083/jcb.147.6.1351
发表时间：
1999-12-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Itoh M;Furuse M;Morita K;Kubota K;Saitou M;Tsukita S
通讯作者：
Tsukita S
影响因子：
3.4
作者：
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通讯作者：
Hecht, G
DOI：
10.1083/jcb.107.4.1575
发表时间：
1988-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gumbiner B;Stevenson B;Grimaldi A
通讯作者：
Grimaldi A
影响因子：
4.8
作者：
Nishiyama, R;Sakaguchi, T;Reinecker, HC
通讯作者：
Reinecker, HC
DOI：
10.1152/ajpgi.2000.279.3.g477
发表时间：
2000-09-01
影响因子：
4.5
作者：
Cereijido, M;Shoshani, L;Contreras, RG
通讯作者：
Contreras, RG