Gehrmann T, Heilmeyer L M
Ruhr-Universität Bochum, Institut für Physiologische Chemie, Abteilung für Biochemie Supramolekularer Systeme, Germany.
Eur J Biochem. 1998 Apr 15;253(2):357-70. doi: 10.1046/j.1432-1327.1998.2530357.x.
Polyphosphoinositides are involved in many signal transduction pathways in eukaryotic cells. The first committed step is catalysed by phosphatidylinositol 4-kinase leading to the formation of phosphatidylinositol 4-phosphate. In the last four years, ten cDNA molecules have been cloned which code isoforms of phosphatidylinositol 4-kinase; some of which are highly related. Characteristically, they contain a C-terminal catalytic domain which is similar to that of (poly)phosphoinositide 3-kinases and to that of more distantly related lipid/protein kinases. Alignment has characterised cDNAs from Chaenorabditis, Dictyostelium and Schizostaphyloccus pombe as those of phosphatidylinositol 4-kinases also. All these lipid kinases are related to the superfamily of protein kinases. Several amino acids are highly conserved in catalytic domains of lipid and protein kinases. Employing the catalytic subunit of the cAMP-dependent protein kinase as template, these residues can be assigned functionally. On the basis of the alignment, a phylogenetic tree of the superfamily of phosphatidylinositol kinases has been constructed. Three families, the phosphatidylinositol 4-kinases, phosphoinositide 3-kinases, and the phosphatidylinositol related lipid/protein kinases, can be recognised. Each family comprises two subfamilies. The involvement of the phosphatidylinositol 4-kinases in signal transduction processes is summarised and a new hypothesis for the function of their isoforms in polyphosphoinositide signalling is presented. The involvement of phosphatidylinositol 4-kinases in formation of lipid-protein interactions with cytoskeleton proteins and the metabolism of polyphosphoinositide in the nucleus is discussed.
多磷酸肌醇参与真核细胞中的许多信号转导途径。第一步关键反应由磷脂酰肌醇4激酶催化，生成磷脂酰肌醇4磷酸。在过去四年中，已克隆出十个编码磷脂酰肌醇4激酶同工型的cDNA分子；其中一些高度相关。其特征在于，它们含有一个C末端催化结构域，该结构域与（多）磷酸肌醇3激酶的催化结构域以及关系更远的脂质/蛋白激酶的催化结构域相似。序列比对表明，来自秀丽隐杆线虫、盘基网柄菌和粟酒裂殖酵母的cDNA也属于磷脂酰肌醇4激酶。所有这些脂质激酶都与蛋白激酶超家族相关。脂质激酶和蛋白激酶的催化结构域中有几个氨基酸高度保守。以cAMP依赖性蛋白激酶的催化亚基为模板，可以对这些残基进行功能赋值。基于序列比对，构建了磷脂酰肌醇激酶超家族的系统发育树。可以识别出三个家族，即磷脂酰肌醇4激酶家族、磷酸肌醇3激酶家族和磷脂酰肌醇相关脂质/蛋白激酶家族。每个家族包括两个亚家族。总结了磷脂酰肌醇4激酶在信号转导过程中的作用，并提出了其同工型在多磷酸肌醇信号传导中功能的新假说。还讨论了磷脂酰肌醇4激酶在与细胞骨架蛋白形成脂质-蛋白相互作用以及细胞核中多磷酸肌醇代谢中的作用。
