A Dictyostelium nuclear phosphatidylinositol phosphate kinase required fordevelopmental gene expression

The generation of diacylglycerol (DAG) in response to receptor stimulation is a well-documented signalling mechanism that leads to activation of prote in kinase C (PKC). Putative alternative effectors contain sequences that in teract with DAGs, but the mechanisms of signal transduction are unknown. We have identified a Dictyosteliumgene encoding a novel protein which contain s 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 re gion. We confirm that the proposed DAG-binding domain is sufficient to medi ate interaction of a fusion protein with vesicles containing DAG. The prote in also shows significant homology to mammalian phosphatidylinositol phosph ate (PIP) kinases and we show that this domain has PIP kinase activity. The protein, PIPkinA, is enriched in the nucleus and abrogation of gene functi on by homologous recombination inhibits early developmental gene expression , blocking development at an early stage. Thus, we have identified a PIP ki nase from Dictyostelium which is required for development, is a candidate e ffector for DAG and has the potential to synthesize nuclear PIP2.