Regulation of anaphylactic responses by phosphatidylinositol phosphate kinase type I α

• Junko Sasaki

  1Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Takehiko Sasaki

  1Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Masakazu Yamazaki

  1Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Kunie Matsuoka

  2Department of Laboratory Animal Science, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Choji Taya

  2Department of Laboratory Animal Science, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Hiroshi Shitara

  2Department of Laboratory Animal Science, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Shunsuke Takasuga

  5Department of Pathology and Immunology, Akita University School of Medicine, Akita 010-8543, Japan

• Miki Nishio

  4Department of Molecular Biology, Akita University School of Medicine, Akita 010-8543, Japan

• Katsunori Mizuno

  1Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Teiji Wada

  8Institute of Molecular and Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria

• Hideyuki Miyazaki

  1Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Hiroshi Watanabe

  1Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Ryota Iizuka

  1Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Shuichi Kubo

  2Department of Laboratory Animal Science, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Shigeo Murata

  3Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Tomoki Chiba

  3Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Tomohiko Maehama

  1Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Koichi Hamada

  4Department of Molecular Biology, Akita University School of Medicine, Akita 010-8543, Japan

• Hiroyuki Kishimoto

  4Department of Molecular Biology, Akita University School of Medicine, Akita 010-8543, Japan

• Michael A. Frohman

  9Center for Developmental Genetics and Department of Pharmacology, State University of New York, Stony Brook, NY 11794

• Keiji Tanaka

  3Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Josef M. Penninger

  8Institute of Molecular and Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria

• Hiromichi Yonekawa

  2Department of Laboratory Animal Science, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

• Akira Suzuki

  4Department of Molecular Biology, Akita University School of Medicine, Akita 010-8543, Japan

• Yasunori Kanaho

  1Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

抄録

The membrane phospholipid phosphatidylinositol 4, 5-bisphosphate [PI(4,5)P2] is a critical signal transducer in eukaryotic cells. However, the physiological roles of the type I phosphatidylinositol phosphate kinases (PIPKIs) that synthesize PI(4,5)P2 are largely unknown. Here, we show that the α isozyme of PIPKI (PIPKIα) negatively regulates mast cell functions and anaphylactic responses. In vitro, PIPKIα-deficient mast cells exhibited increased degranulation and cytokine production after Fcε receptor-I cross-linking. In vivo, PIPKIα−/− mice displayed enhanced passive cutaneous and systemic anaphylaxis. Filamentous actin was diminished in PIPKIα−/− mast cells, and enhanced degranulation observed in the absence of PIPKIα was also seen in wild-type mast cells treated with latrunculin, a pharmacological inhibitor of actin polymerization. Moreover, the association of FcεRI with lipid rafts and FcεRI-mediated activation of signaling proteins was augmented in PIPKIα−/− mast cells. Thus, PIPKIα is a negative regulator of FcεRI-mediated cellular responses and anaphylaxis, which functions by controlling the actin cytoskeleton and dynamics of FcεRI signaling. Our results indicate that the different PIPKI isoforms might be functionally specialized.

収録刊行物

• The Journal of Experimental Medicine

  The Journal of Experimental Medicine 201 (6), 859-870, 2005-03-14

  Rockefeller University Press

キーワード

• Immunology
• Immunology and Allergy

詳細情報

• CRID: 1363388845343321600
• NII論文ID: 30017434622
• DOI: 10.1084/jem.20041891
• ISSN: 15409538
• ISSN: 00221007
• ISSN: http://id.crossref.org/issn/00221007
• Web Site: https://rupress.org/jem/article-pdf/201/6/859/1717674/jem2016859.pdf
• データソース種別:
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