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J Biol Chem, Vol. 273, Issue 20, 12407-12414, May 15, 1998
Structural and Functional Properties of Complement-activating
Protein M161Ag, a Mycoplasma fermentans Gene Product That
Induces Cytokine Production by Human Monocytes
Misako
Matsumoto ,
Miyuki
Nishiguchi ,
Satomi
Kikkawa ,
Hitoshi
Nishimura§,
Shigeharu
Nagasawa§, and
Tsukasa
Seya ¶
From the Department of Immunology, Osaka Medical
Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka
537, the § Department of Pharmaceutical Sciences, Hokkaido
University, Kita-ku, Sapporo 060, and ¶ PRESTO, JST, Tokyo 105, Japan
Human malignant cells are targeted by homologous
complement C3b if they express M161Ag, a 43-kDa protein with
C3-activating property. cDNA of M161Ag cloned from human leukemia
cell lines predicted M161Ag as a novel secretory protein comprised of
428 amino acids including 5 amino acids encoded by TGA codons
(Matsumoto M., Takeda, J., Inoue, N., Hara, T., Hatanaka, M.,
Takahashi, K., Nagasawa, S., Akedo, H., and Seya, T. (1997) Nat.
Med. 3, 1266-1270), although the origin of this gene was
obscure. Here we clarified this point through genomic and biochemical
analysis: 1) 5'-UT and genomic sequences represented the prokaryote
promoter and ribosomal binding site; 2) the TGA codons in M161Ag
cDNA were translated not into selenocysteines but into tryptophans;
3) M161Ag anchored onto the membrane secondary to its N-terminal
palmitoylation like prokaryote lipoproteins; 4) genomic and cDNA
clones of M161Ag were highly homologous to Mycoplasma
fermentans gene encoding P48, a monocytic
differentiation/activation factor, recently released in the data base,
although the resultant proteins were different in the amino acid
sequences. Additionally, purified soluble M161Ag efficiently provoked
IL-1 , tumor necrosis factor , and IL-6 like P48, and further
IL-10 and IL-12 in human peripheral blood monocytes. Thus, M161Ag
originates from M. fermentans, and latently infected
M. fermentans allows human cells to produce M161Ag. The liberated protein serves as a potent modulator of innate and cellular immune responses via its complement-activating and cytokine-producing activities.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1998 by the American Society for Biochemistry and Molecular Biology.
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