Regulation of anaphylactic responses by phosphatidylinositol phosphate kinase type I α

• DOI: 10.1084/jem.20041891
• Publication Date: 2005-03-15T01:26:02Z
• Authors: Junko Sasaki; Takehiko Sasaki; Masakazu Yamazaki; Kunie Matsuoka; Choji Taya; Hiroshi Shitara; Shunsuke Takasuga; Miki Nishio; Katsunori Mizuno; Teiji Wada; Hideyuki Miyazaki; Hiroshi Watanabe; Ryota Iizuka; Shuichi Kubo; Shigeo Murata; Tomoki Chiba; Tomohiko Maehama; Koichi Hamada; Hiroyuki Kishimoto; Michael A. Frohman; Keiji Tanaka; Josef M. Penninger; Hiromichi Yonekawa; Akira Suzuki; Yasunori Kanaho
• Keywords: Mice, Knockout; Phosphatidylinositol 4,5-Diphosphate; 0303 health sciences; Receptors, IgE; Article; Actins; Cell Degranulation; Isoenzymes; Minor Histocompatibility Antigens; Mice; Phosphotransferases (Alcohol Group Acceptor); Thiazoles; 03 medical and health sciences; Membrane Microdomains; Animals; Calcium Signaling; Mast Cells; Anaphylaxis; Cells, Cultured

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