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Diacylglycerol kinase zeta regulates phosphatidylinositol 4-phosphate 5-kinase Ialpha by a novel mechanism.
Cell Signal. 2004 Aug; 16(8):891-7.CS

Abstract

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.

Authors+Show Affiliations

Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15157668

Citation

Luo, Bai, et al. "Diacylglycerol Kinase Zeta Regulates Phosphatidylinositol 4-phosphate 5-kinase Ialpha By a Novel Mechanism." Cellular Signalling, vol. 16, no. 8, 2004, pp. 891-7.
Luo B, Prescott SM, Topham MK. Diacylglycerol kinase zeta regulates phosphatidylinositol 4-phosphate 5-kinase Ialpha by a novel mechanism. Cell Signal. 2004;16(8):891-7.
Luo, B., Prescott, S. M., & Topham, M. K. (2004). Diacylglycerol kinase zeta regulates phosphatidylinositol 4-phosphate 5-kinase Ialpha by a novel mechanism. Cellular Signalling, 16(8), 891-7.
Luo B, Prescott SM, Topham MK. Diacylglycerol Kinase Zeta Regulates Phosphatidylinositol 4-phosphate 5-kinase Ialpha By a Novel Mechanism. Cell Signal. 2004;16(8):891-7. PubMed PMID: 15157668.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diacylglycerol kinase zeta regulates phosphatidylinositol 4-phosphate 5-kinase Ialpha by a novel mechanism. AU - Luo,Bai, AU - Prescott,Stephen M, AU - Topham,Matthew K, PY - 2003/12/08/received PY - 2004/01/08/accepted PY - 2004/5/26/pubmed PY - 2005/5/20/medline PY - 2004/5/26/entrez SP - 891 EP - 7 JF - Cellular signalling JO - Cell Signal VL - 16 IS - 8 N2 - 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. SN - 0898-6568 UR - https://www.unboundmedicine.com/medline/citation/15157668/Diacylglycerol_kinase_zeta_regulates_phosphatidylinositol_4_phosphate_5_kinase_Ialpha_by_a_novel_mechanism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0898656804000130 DB - PRIME DP - Unbound Medicine ER -