title: Phosphatidylinositol 4-kinases.
abstract: 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.
authors.affiliation: Ruhr-Universität Bochum, Institut für Physiologische Chemie, Abteilung für Biochemie Supramolekularer Systeme, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Gehrmann
authors.forename: L M
authors.initials: LM
authors.lastname: Heilmeyer
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002467:Cell Nucleus / Q000201:enzymology; D003599:Cytoskeleton / Q000201:enzymology; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D011494:Protein Kinases; D019870:1-Phosphatidylinositol 4-Kinase