Phosphatidylinositol 4-Phosphate 5-Kinase α Is a Downstream Effector of the Small G Protein ARF6 in Membrane Ruffle Formation
| Autor: | Hiroshi Nakamura, Kazumasa Kawamoto, Akira Honda, Hiroshi Watanabe, Yasunori Kanaho, Michael A. Frohman, Andrew J. Morris, Takeaki Yokozeki, Masahiro Nogami, Kazuhisa Nakayama, Masakazu Yamazaki |
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| Rok vydání: | 1999 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate RHOA Phosphatidylinositol 4-phosphate Molecular Sequence Data Phosphatidic Acids General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Phospholipase D Animals Amino Acid Sequence Phosphatidylinositol Sequence Homology Amino Acid biology ADP-Ribosylation Factors Biochemistry Genetics and Molecular Biology(all) PLD2 Cell Membrane Biological Transport Phosphatidic acid Cell Compartmentation Cell biology Enzyme Activation Isoenzymes Pleckstrin homology domain Phosphotransferases (Alcohol Group Acceptor) chemistry ADP-Ribosylation Factor 6 Guanosine 5'-O-(3-Thiotriphosphate) biology.protein Phosphatidylinositol phosphate kinases ADP-Ribosylation Factor 1 Cattle Signal Transduction |
| Zdroj: | Cell. 99:521-532 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/s0092-8674(00)81540-8 |
| Popis: | Synthesis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], a signaling phospholipid, is primarily carried out by phosphatidylinositol 4-phosphate 5-kinase [PI(4)P5K], which has been reported to be regulated by RhoA and Rac1. Unexpectedly, we find that the GTPgammaS-dependent activator of PI(4)P5Kalpha is the small G protein ADP-ribosylation factor (ARF) and that the activation strictly requires phosphatidic acid, the product of phospholipase D (PLD). In vivo, ARF6, but not ARF1 or ARF5, spatially coincides with PI(4)P5Kalpha. This colocalization occurs in ruffling membranes formed upon AIF4 and EGF stimulation and is blocked by dominant-negative ARF6. PLD2 similarly translocates to the ruffles, as does the PH domain of phospholipase Cdelta1, indicating locally elevated PI(4,5)P2. Thus, PI(4)P5Kalpha is a downstream effector of ARF6 and when ARF6 is activated by agonist stimulation, it triggers recruitment of a diverse but interactive set of signaling molecules into sites of active cytoskeletal and membrane rearrangement. |
| Databáze: | OpenAIRE |
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