RGD Reference Report - Diacylglycerol kinase zeta regulates phosphatidylinositol 4-phosphate 5-kinase Ialpha by a novel mechanism. - Rat Genome Database

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Diacylglycerol kinase zeta regulates phosphatidylinositol 4-phosphate 5-kinase Ialpha by a novel mechanism.

Authors: Luo, Bai  Prescott, Stephen M  Topham, Matthew K 
Citation: Luo B, etal., Cell Signal. 2004 Aug;16(8):891-7. doi: 10.1016/j.cellsig.2004.01.010.
RGD ID: 13792527
Pubmed: PMID:15157668   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cellsig.2004.01.010   (Journal Full-text)

Phosphatidylinositol 4,5-bisphosphate (PIP2) plays an important role during actin polymerization and is produced by the type I phosphatidylinositol 4-phosphate 5-kinases (PIP5KI), which are activated by phosphatidic acid (PA). As diacylglycerol kinases (DGKs) generate PA by phosphorylating diacylglycerol (DAG), we investigated whether DGKs were involved in controlling PIP2 levels by regulating PIP5KI activity. Here we show that expression of DGKzeta significantly enhances PIP5KIalpha activity in thrombin-stimulated HEK293 cells, and DGK activity is required for this stimulation. We also observed that DGKzeta co-immunoprecipitated and co-localized with PIP5KIalpha, suggesting that they reside in a regulated signaling complex. To explore the role of DGKzeta in actin polymerization, we examined the subcellular distribution of DGKzeta, PIP5KIalpha and actin, and found that these proteins co-localized with actin in lamellipodial protrusions. Supporting that PIP5KIalpha regulation occurs at the sites of actin polymerization, we found that PIP2 also accumulated in the actin-rich regions of lamellipodia. Significantly, in wounding assays, DGKzeta, PIP5KIalpha and PIP2 accumulated at the leading edge of migrating A172 cells, where massive actin polymerization is known to occur. Combined, these data support a novel function for DGKzeta: by generating PA, it stimulates PIP5KIalpha activity to increase local PIP2, which regulates actin polymerization.




Molecular Function

  
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Species
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Evidence
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Original Reference(s)
DgkzRatprotein binding enablesIPIUniProtKB:D3ZSI8PMID:15157668UniProt 
Pip5k1aRatprotein binding enablesIPIUniProtKB:O08560PMID:15157668UniProt 


Genes (Rattus norvegicus)
Dgkz  (diacylglycerol kinase zeta) Pip5k1a  (phosphatidylinositol-4-phosphate 5-kinase, type 1, alpha)