Mammalian Phosphatidylinositol 4‐Kinases

Three phosphatidylinositol 4‐kinase isoforms, PI4K 230, 92 and 55 have been cloned and sequenced allowing a much wider characterization than the previously employed enzymological typing into type II and III enzymes. PI4K 230 and 92 contain a highly conserved catalytic core, PI4K55 one with a much lo...

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Bibliographic Details
Published in:IUBMB life 2003-02, Vol.55 (2), p.59-65
Main Authors: Heilmeyer, Ludwig M. G., Szivák, Ilona, Vereb, György, Kakuk, Annamária
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 4-Kinase - genetics
1-Phosphatidylinositol 4-Kinase - metabolism
Animals
Brefeldin A
Humans
Leptomycin B
nuclear localization and export signals
nucleolar localization
Phosphatidylinositol 4‐Kinase isoforms
Protein Isoforms
Rats
vesicular transport
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Summary:Three phosphatidylinositol 4‐kinase isoforms, PI4K 230, 92 and 55 have been cloned and sequenced allowing a much wider characterization than the previously employed enzymological typing into type II and III enzymes. PI4K 230 and 92 contain a highly conserved catalytic core, PI4K55 one with a much lower degree of similarity. Candidate kinase motifs, deduced from the protein kinase super family, are absolutely conserved in all isoforms. Kinase activities are described based on their sensitivity and reactivity towards wortmannin, phenylarsine oxide (PAO) and 5′‐p‐fluorosulfonylbenzoyladenosine (FSBA). Localization of all isoforms in the cell is reported. All enzymes contain nuclear localization and export sequence motifs (NLS and NES) leading to the expectation that they can be transferred to the nucleus. PI4K230 has been found in the nucleolus, PI4K92 in the nucleus, additionally further broadening the function of these enzymes. In the cytoplasm of neuronal cells, PI4K230 is distributed evenly on membranes that are ultra structurally cisterns of the rough endoplasmatic reticulum, outer membranes of mitochondria, multivesicular bodies, and are in close vicinity of synaptic contacts. PI4K92 is functionally characterized as a key enzyme regulating Golgi disintegration/reorganization during mitosis probably via phosphorylation by cyclin‐dependent kinases on well‐defined sites. PI4K55 is involved in the production of second messengers, diacylglycerol (DAG) and inositol 1,4,5‐trisphosphate (InsP3) at the plasma membrane, moreover, in the endocytotic pathway in the cytoplasm.
ISSN:1521-6543
1521-6551
DOI:10.1002/tbmb.718540873