Phosphatidylinositol 4-phosphate 5-kinase α is a downstream effector of the small G protein ARF6 in membrane ruffle formation

Akira Honda; Masahiro Nogami; Takeaki Yokozeki; Masakazu Yamazaki; Hiroshi Nakamura; Hiroshi Watanabe; Kazumasa Kawamoto; Kazuhisa Nakayama; Andrew J. Morris; Michael A. Frohman; Yasunori Kanaho

doi:10.1016/S0092-8674(00)81540-8

Phosphatidylinositol 4-phosphate 5-kinase α is a downstream effector of the small G protein ARF6 in membrane ruffle formation

Akira Honda, Masahiro Nogami, Takeaki Yokozeki, Masakazu Yamazaki, Hiroshi Nakamura, Hiroshi Watanabe, Kazumasa Kawamoto, Kazuhisa Nakayama, Andrew J. Morris, Michael A. Frohman, Yasunori Kanaho

Internal Medicine

Research output: Contribution to journal › Article › peer-review

720 Scopus citations

Abstract

Synthesis of phosphatidylinositol 4,5-bisphosphate [Pl(4,5)P₂], a signaling phospholipid, is primarily carried out by phosphatidylinositol 4- phosphate 5-kinase [Pl(4)P5K], which has been reported to be regulated by RhoA and Rac1. Unexpectedly, we find that the GTPγ/S-dependent activator of Pl(4)P5Kα 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 Pl(4)P5Kα. This colocalization occurs in ruffling membranes formed upon AlF₄ and EGF stimulation and is blocked by dominant-negative ARF6. PLD2 similarly translocates to the ruffles, as does the PH domain of phospholipase Cδ1, indicating locally elevated Pl(4,5)P₂. Thus, Pl(4)P5Kα 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.

Original language	English
Pages (from-to)	521-532
Number of pages	12
Journal	Cell
Volume	99
Issue number	5
DOIs	https://doi.org/10.1016/S0092-8674(00)81540-8
State	Published - Nov 24 1999

Bibliographical note

Funding Information:
We are grateful to Drs. U. Kikkawa, Y. Kaziro, J. I. Gordon, and K. Toda for providing pTB701-FLAG, Rac1 G12V and the Rac1 T17N, pBB131 plasmids, and ARF plasmids, respectively. We also thank Drs. H. Yagisawa, M. Fujii, and T. Osumi for providing GFP-PH/PLCδ1, Dr. M. Umeda for the anti-PI(4,5)P 2 antibody, and Dr. H. Taguchi for skillful support in the sequencing of the purified GTPγS-dependent activator of PI(4)P5Kα. This study was supported by research grant from the Ministry of Education, Science, Sports and Culture, Japan to Y. K. and grants from the NIH to A. J. M. (GM50388) and M. A. F. (GM54813). T. Y. and M. Y. are Research Fellows of the Japan Society for the Promotion of Science.

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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@article{931a4ea3a1a3494c8883dc354f0d52a8,

title = "Phosphatidylinositol 4-phosphate 5-kinase α is a downstream effector of the small G protein ARF6 in membrane ruffle formation",

abstract = "Synthesis of phosphatidylinositol 4,5-bisphosphate [Pl(4,5)P2], a signaling phospholipid, is primarily carried out by phosphatidylinositol 4- phosphate 5-kinase [Pl(4)P5K], which has been reported to be regulated by RhoA and Rac1. Unexpectedly, we find that the GTPγ/S-dependent activator of Pl(4)P5Kα 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 Pl(4)P5Kα. This colocalization occurs in ruffling membranes formed upon AlF4 and EGF stimulation and is blocked by dominant-negative ARF6. PLD2 similarly translocates to the ruffles, as does the PH domain of phospholipase Cδ1, indicating locally elevated Pl(4,5)P2. Thus, Pl(4)P5Kα 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.",

author = "Akira Honda and Masahiro Nogami and Takeaki Yokozeki and Masakazu Yamazaki and Hiroshi Nakamura and Hiroshi Watanabe and Kazumasa Kawamoto and Kazuhisa Nakayama and Morris, {Andrew J.} and Frohman, {Michael A.} and Yasunori Kanaho",

note = "Funding Information: We are grateful to Drs. U. Kikkawa, Y. Kaziro, J. I. Gordon, and K. Toda for providing pTB701-FLAG, Rac1 G12V and the Rac1 T17N, pBB131 plasmids, and ARF plasmids, respectively. We also thank Drs. H. Yagisawa, M. Fujii, and T. Osumi for providing GFP-PH/PLCδ1, Dr. M. Umeda for the anti-PI(4,5)P 2 antibody, and Dr. H. Taguchi for skillful support in the sequencing of the purified GTPγS-dependent activator of PI(4)P5Kα. This study was supported by research grant from the Ministry of Education, Science, Sports and Culture, Japan to Y. K. and grants from the NIH to A. J. M. (GM50388) and M. A. F. (GM54813). T. Y. and M. Y. are Research Fellows of the Japan Society for the Promotion of Science.",

year = "1999",

month = nov,

day = "24",

doi = "10.1016/S0092-8674(00)81540-8",

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pages = "521--532",

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T1 - Phosphatidylinositol 4-phosphate 5-kinase α is a downstream effector of the small G protein ARF6 in membrane ruffle formation

AU - Honda, Akira

AU - Nogami, Masahiro

AU - Yokozeki, Takeaki

AU - Yamazaki, Masakazu

AU - Nakamura, Hiroshi

AU - Watanabe, Hiroshi

AU - Kawamoto, Kazumasa

AU - Nakayama, Kazuhisa

AU - Morris, Andrew J.

AU - Frohman, Michael A.

AU - Kanaho, Yasunori

N1 - Funding Information: We are grateful to Drs. U. Kikkawa, Y. Kaziro, J. I. Gordon, and K. Toda for providing pTB701-FLAG, Rac1 G12V and the Rac1 T17N, pBB131 plasmids, and ARF plasmids, respectively. We also thank Drs. H. Yagisawa, M. Fujii, and T. Osumi for providing GFP-PH/PLCδ1, Dr. M. Umeda for the anti-PI(4,5)P 2 antibody, and Dr. H. Taguchi for skillful support in the sequencing of the purified GTPγS-dependent activator of PI(4)P5Kα. This study was supported by research grant from the Ministry of Education, Science, Sports and Culture, Japan to Y. K. and grants from the NIH to A. J. M. (GM50388) and M. A. F. (GM54813). T. Y. and M. Y. are Research Fellows of the Japan Society for the Promotion of Science.

PY - 1999/11/24

Y1 - 1999/11/24

N2 - Synthesis of phosphatidylinositol 4,5-bisphosphate [Pl(4,5)P2], a signaling phospholipid, is primarily carried out by phosphatidylinositol 4- phosphate 5-kinase [Pl(4)P5K], which has been reported to be regulated by RhoA and Rac1. Unexpectedly, we find that the GTPγ/S-dependent activator of Pl(4)P5Kα 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 Pl(4)P5Kα. This colocalization occurs in ruffling membranes formed upon AlF4 and EGF stimulation and is blocked by dominant-negative ARF6. PLD2 similarly translocates to the ruffles, as does the PH domain of phospholipase Cδ1, indicating locally elevated Pl(4,5)P2. Thus, Pl(4)P5Kα 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.

AB - Synthesis of phosphatidylinositol 4,5-bisphosphate [Pl(4,5)P2], a signaling phospholipid, is primarily carried out by phosphatidylinositol 4- phosphate 5-kinase [Pl(4)P5K], which has been reported to be regulated by RhoA and Rac1. Unexpectedly, we find that the GTPγ/S-dependent activator of Pl(4)P5Kα 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 Pl(4)P5Kα. This colocalization occurs in ruffling membranes formed upon AlF4 and EGF stimulation and is blocked by dominant-negative ARF6. PLD2 similarly translocates to the ruffles, as does the PH domain of phospholipase Cδ1, indicating locally elevated Pl(4,5)P2. Thus, Pl(4)P5Kα 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.

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Phosphatidylinositol 4-phosphate 5-kinase α is a downstream effector of the small G protein ARF6 in membrane ruffle formation

Abstract

Bibliographical note

ASJC Scopus subject areas

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