Polyphosphoinositides are involved in many signal transduction pathway
s in eukaryotic cells. The first committed step is catalysed by phosph
atidylinositol 4-kinase leading to the formation of phosphatidylinosit
ol 4-phosphate. In the last four years, ten cDNA molecules have been c
loned which code isoforms of phosphatidylinositol 4-kinase: some of wh
ich 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. A
lignment has characterised cDNAs from Caenorhabditis, Dictyostelium an
d Schizostaphyloccus pombe as those of phosphatidylinositol 4-kinases
also. All these lipid kinases are related to the superfamily of protei
n kinases. Several amino acids are highly conserved in catalytic domai
ns of lipid and protein kinases. Employing the catalytic subunit of th
e cAMP-dependent protein kinase as template, these residues can be ass
igned functionally. On the basis of the alignment, a phylogenetic tree
of the superfamily of phosphatidylinositol kinases has been construct
ed. Three families, the phosphatidylinositol 4-kinases, phosphoinositi
de 3-kinases, and the phosphatidylinositol related lipid/protein kinas
es, carl be recognised. Each family comprises two subfamilies. The inv
olvement 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 involve
ment of phosphatidylinositol 4-kinases in formation of lipid-protein i
nteractions with cytoskeleton proteins and the metabolism of polyphosp
hoinositide in the nucleus is discussed.