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A Dictyostelium nuclear phosphatidylinositol phosphate kinase required for developmental gene expression
Author(s) -
Guo Kunde,
Nichol Richard,
Skehel Paul,
Dormann Dirk,
Weijer Cornelis J.,
Williams Jeffrey G.,
Pears Catherine
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.21.6017
Subject(s) - biology , diacylglycerol kinase , pleckstrin homology domain , protein kinase c , effector , dictyostelium , microbiology and biotechnology , protein kinase domain , phosphatidylinositol , signal transduction , kinase , sh3 domain , gene , genetics , proto oncogene tyrosine protein kinase src , mutant
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 .