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J. Biochem, 2003, Vol. 134, No. 5 699-709
© 2003 Japanese Biochemical Society

BIOCHEMISTRY

Induction of PYPAF1 during In Vitro Maturation of Mouse Mast Cells

Rei Kikuchi-Yanoshita1, Yoshitaka Taketomi1, Kumiko Koga1, Toshihiko Sugiki1, Yohei Atsumi1, Takanori Saito1, Shin-ichi Ishii2, Masato Hisada2, Tamiko Suzuki-Nishimura2, Masaatsu K. Uchida2, Tae-Chul Moon3, Hyeun-Wook Chang3, Masatsugu Sawada4, Naoki Inagaki4, Hiroichi Nagai4, Makoto Murakami*,1 and Ichiro Kudo1

1 Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555; 2 Department of Pharmacology, Meiji Pharmaceutical University, 2-522-1 Nishio, Kiyose, Tokyo 204-8588; 3 College of Pharmacy, Yeungnam University, Gyonsan, Korea; and 4 Pharmacological Department, Gifu College of Pharmacy, 5-6-1 Mitahora Higashi, Gifu 502-8585

Coculture of mouse bone marrow-derived immature mast cells (BMMC) with Swiss 3T3 fibroblasts in the presence of stem cell factor (SCF) promotes morphological and functional maturation toward a connective tissue mast cell (CTMC)–like phenotype, which is accompanied by increased expression of several unique genes. Here we report the molecular identification of one of them, mast cell maturation–associated inducible gene (MMIG)-1. The MMIG-1 cDNA encodes a 117-kDa cytosolic protein that comprises an N-terminal PYRIN domain, a central nucleotide-binding domain, and nine C-terminal leucine-rich repeats. MMIG-1 shows >85% sequence similarity to human cryopyrin/PYPAF1, a causal gene for familial cold urticaria and Muckle-Wells syndrome. MMIG-1 was distributed in the cytosol of CTMC-like differentiated BMMC. MMIG-1 underwent alternative splicing in the leucine-rich repeats and each variant was induced differently in BMMC during coculture. Moreover, its expression was increased in the ears of mice with experimental atopic dermatitis. Thus, MMIG-1, a likely mouse PYPAF1 ortholog, may play a role in mast cell–directed inflammatory diseases.

* To whom correspondence should be addressed. Tel: +81-3-3784-8196, Fax: +81-3-3784-8245, E-mail: mako{at}pharm.showa-u.ac.jp


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