A polarity complex of mPar-6 and atypical PKC binds, phosphorylates and regulates mammalian Lgl
A polarity complex of mPar-6 and atypical PKC binds, phosphorylates and regulates mammalian Lgl
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DOI：
10.1038/ncb948
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发表时间：
2003-04-01
影响因子：
21.3
通讯作者：
Pawson, T
中科院分区：
文献类型：
--
作者：
Plant, PJ;Fawcett, JP;Pawson, T
进化上保守的蛋白PAR-6、非典型蛋白激酶C(APKC)、CDC42和PAR-3共同调节细胞的极性和不对称的细胞分裂，但该复合体的下游靶点很大程度上是未知的。在这里，我们确定了哺乳动物aPKC、小鼠PAR-6C(mPar-6C)和Mlgl之间的直接生理相互作用，Mlg1是果蝇黑腹肿瘤抑制因子致死(2)巨型幼虫的哺乳动物同源基因。在培养的细胞系和小鼠脑中，aPKC、mPar-6C和Mlg1形成一个多蛋白复合体，其中Mlg1被靶向保守的丝氨酸残基的磷酸化。这些磷酸化位点对于胚胎成纤维细胞在创伤反应中正确极化是重要的，并可能调节Mlg1引导蛋白质运输的能力。我们的数据提供了不同极性复合体的蛋白质之间的直接物理和调控联系，确认Mlg1是细胞极化中aPKC的功能底物，并表明aPKC通过蛋白质-蛋白质相互作用网络定向到细胞极性底物。
The evolutionarily conserved proteins Par-6, atypical protein kinase C (aPKC), Cdc42 and Par-3 associate to regulate cell polarity and asymmetric cell division, but the downstream targets of this complex are largely unknown. Here we identify direct physiological interactions between mammalian aPKC, murine Par-6C (mPar-6C) and Mlgl, the mammalian orthologue of the Drosophila melanogaster tumour suppressor Lethal (2) giant larvae. In cultured cell lines and in mouse brain, aPKC, mPar-6C and Mlgl form a multiprotein complex in which Mlgl is targeted for phosphorylation on conserved serine residues. These phosphorylation sites are important for embryonic fibroblasts to polarize correctly in response to wounding and may regulate the ability of Mlgl to direct protein trafficking. Our data provide a direct physical and regulatory link between proteins of distinct polarity complexes, identify Mlgl as a functional substrate for aPKC in cell polarization and indicate that aPKC is directed to cell polarity substrates through a network of protein-protein interactions.