Association of protein kinase c μ with type II phosphatidylinositol 4-kinase and type I phosphatidylinositol-4-phosphate 5-kinase
Association of protein kinase c μ with type II phosphatidylinositol 4-kinase and type I phosphatidylinositol-4-phosphate 5-kinase
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DOI：
10.1074/jbc.273.36.23126
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发表时间：
1998-09-04
影响因子：
4.8
通讯作者：
Cantley, LC
中科院分区：
文献类型：
--
作者：
Nishikawa, K;Toker, A;Cantley, LC
蛋白激酶C μ（Protein kinase C mu，PKC mu）又称蛋白激酶D（protein kinase D），是PKC家族中一个不常见的成员，具有跨膜结构域和普列克底物蛋白同源结构域。这种酶具有不同于其它PKC同种型的底物特异性（Nishikawa，K.，Toker，A.，Johannes，F. J.，松阳，Z.，和Cantley，L. C.（1997）J.Biol.Chem.272，952-960），并且其调节机制尚不清楚。在这里，我们表明，PKC μ形成一个复杂的磷脂酰肌醇4-激酶和磷脂酰肌醇-4-磷酸5-激酶在体内。氨基末端跨膜结构域和普列克底物蛋白同源结构域之间的PKC μ区域被证明参与与脂质激酶的关联。有趣的是，PKC μ.未能与任一脂质激酶活性相关，表明可能需要自磷酸化来暴露脂质激酶相互作用结构域。此外，PKC μ-相关的脂质激酶的亚细胞分布的颗粒部分取决于氨基末端的存在。包括预测的跨膜区的PKC μ的区域。这些结果表明，一种新的模型中，PKC μ的非催化区域作为一个支架组装的酶参与磷酸肌醇合成在特定的膜位置。
Protein kinase C mu (PKC mu), also named protein kinase D, is an unusual member of the PKC family that has a putative transmembrane domain and pleckstrin homology domain. This enzyme has a substrate specificity distinct from other PKC isoforms (Nishikawa, K., Toker, A., Johannes, F. J., Songyang, Z., and Cantley, L. C. (1997) J. Biol. Chem. 272, 952-960), and its mechanism of regulation is not yet clear. Here we show that PKC mu forms a complex in vivo with a phosphatidylinositol 4-kinase and a phosphatidylinositol-4-phosphate 5-kinase. A region of PKC mu between the amino-terminal transmembrane domain and the pleckstrin homology domain is shown to be involved in the association with the lipid kinases. Interestingly, a kinase-dead point mutant of PKC mu. failed to associate with either lipid kinase activity, indicating that autophosphorylation may be required to expose the Lipid kinase interaction domain. Furthermore, the subcellular distribution of the PKC mu-associated lipid kinases to the particulate fraction depends on the presence of the amino-terminal. region of PKC mu including the predicted transmembrane region. These results suggest a novel model in which the noncatalytic region of PKC mu acts as a scaffold for assembly of enzymes involved in phosphoinositide synthesis at specific membrane locations.