Interaction of the Type Ialpha PIPkinase with phospholipase D: a role for the local generation of phosphatidylinositol 4,5-bisphosphate in the regulation of PLD2 activity
| Autor: | Mieke Roefs, Michael J.O. Wakelam, Nullin Divecha, Sabine d'Andrea, Kahlid M. Saqib, Mar Fernandez‐Borga, L. C. J. M. Oomen, Jonathan R. Halstead, Clive D'Santos |
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| Rok vydání: | 2000 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate Swine Recombinant Fusion Proteins Phospholipase Biology Transfection Gene Expression Regulation Enzymologic General Biochemistry Genetics and Molecular Biology Mice chemistry.chemical_compound Genes Reporter Phospholipase D Animals Phosphatidylinositol Molecular Biology Aorta Cells Cultured Sequence Deletion General Immunology and Microbiology General Neuroscience PLD2 Articles Phosphatidic acid Immunohistochemistry Precipitin Tests Cell biology Enzyme Activation Phosphotransferases (Alcohol Group Acceptor) Phosphatidylinositol 4 5-bisphosphate chemistry Biochemistry COS Cells Second messenger system Tetradecanoylphorbol Acetate lipids (amino acids peptides and proteins) Endothelium Vascular Intracellular Protein Binding |
| Zdroj: | The EMBO Journal. 19:5440-5449 |
| ISSN: | 1460-2075 |
| DOI: | 10.1093/emboj/19.20.5440 |
| Popis: | Phosphoinositides are localized in various intracellular compartments and can regulate a number of intracellular functions, such as cytoskeletal dynamics and membrane trafficking. Phospholipase Ds (PLDs) are regulated enzymes that hydrolyse phosphatidylcholine (PtdCho) to generate the putative second messenger phosphatidic acid (PtdOH). In vitro, PLDs have an absolute requirement for higher phosphorylated inositides, such as phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)]. Whether this lipid is able to regulate the activity of PLD in vivo is contentious. To examine this hypothesis we studied the relationship between PLD and an enzyme critical for the intracellular synthesis of PtdIns(4,5)P(2): phosphatidylinositol 4-phosphate 5-kinase alpha (Type Ialpha PIPkinase). We find that both PLD1 and PLD2 interact with the Type Ialpha PIPkinase and that PLD2 activity in vivo can be regulated solely by the expression of this lipid kinase. Moreover, PLD2 is able to recruit the Type Ialpha PIPkinase to its intracellular location. We show that the physiological requirement of PLD enzymes for PtdIns(4,5)P(2) is critical and that PLD2 activity can be regulated solely by the levels of this key intracellular lipid. |
| Databáze: | OpenAIRE |
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