title: A Dictyostelium nuclear phosphatidylinositol phosphate kinase required for developmental gene expression.
abstract: The generation of diacylglycerol (DAG) in response to receptor stimulation is a well-documented signalling mechanism that leads to activation of protein kinase C (PKC). Putative alternative effectors contain sequences that interact with DAGs, but the mechanisms of signal transduction are unknown. We have identified a Dictyostelium gene encoding a novel protein which contains a domain with high identity to the DAG-binding domain of PKC. It does not encode a PKC homologue as the conservation does not extend outside this region. We confirm that the proposed DAG-binding domain is sufficient to mediate interaction of a fusion protein with vesicles containing DAG. The protein also shows significant homology to mammalian phosphatidylinositol phosphate (PIP) kinases and we show that this domain has PIP kinase activity. The protein, PIPkinA, is enriched in the nucleus and abrogation of gene function by homologous recombination inhibits early developmental gene expression, blocking development at an early stage. Thus, we have identified a PIP kinase from Dictyostelium which is required for development, is a candidate effector for DAG and has the potential to synthesize nuclear PIP(2).
authors.affiliation: Department of Biochemistry, Oxford University, South Parks Road, Oxford OX1, UK.
authors.forename: K
authors.initials: K
authors.lastname: Guo
authors.forename: R
authors.initials: R
authors.lastname: Nichol
authors.forename: P
authors.initials: P
authors.lastname: Skehel
authors.forename: D
authors.initials: D
authors.lastname: Dormann
authors.forename: C J
authors.initials: CJ
authors.lastname: Weijer
authors.forename: J G
authors.initials: JG
authors.lastname: Williams
authors.forename: C
authors.initials: C
authors.lastname: Pears
mesh_terms: D000818:Animals; D002449:Cell Aggregation / Q000502:physiology; D002467:Cell Nucleus / Q000201:enzymology*; D017124:Conserved Sequence; D004023:Dictyostelium / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development; D004075:Diglycerides / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
chemical_list: D004075:Diglycerides; C440003:PIPkinA protein, Dictyostelium discoideum; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase