title: NFAM1, an immunoreceptor tyrosine-based activation motif-bearing molecule that regulates B cell development and signaling.
abstract: A functional cDNA cloning system was developed by using a retrovirus library encoding CD8-chimeric proteins and a nuclear factor of activated T cells (NFAT)-GFP reporter cell line to identify molecules inducing NFAT activation. By using this strategy, NFAT activating molecule 1 (NFAM1) was cloned as an immunoreceptor tyrosine-based activation motif (ITAM)-bearing cell surface molecule belonging to the Ig superfamily and is predominantly expressed in spleen B and T cells. NFAM1 crosslinking induced ITAM phosphorylation, ZAP-70/Syk recruitment, NFAT activation, and cytokine production. In vivo overexpression of NFAM1 in bone marrow chimeras and transgenic mice induced severe impairment of early B cell development in an ITAM-dependent manner. In NFAM1-expressing B cells, B cell antigen receptor stimulation induced NFAM1 translocation to lipid raft, and NFAM1 co-crosslinking augmented B cell antigen receptor signaling. The results suggest that NFAM1 modulates B cell signaling through its ITAM, which regulates B cell development.
authors.affiliation: Department of Molecular Genetics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohtsuka
authors.forename: Hisashi
authors.initials: H
authors.lastname: Arase
authors.forename: Arata
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Shiina
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Suenaga
authors.forename: Daiju
authors.initials: D
authors.lastname: Sakurai
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yokosuka
authors.forename: Noriko
authors.initials: N
authors.lastname: Arase
authors.forename: Makio
authors.initials: M
authors.lastname: Iwashima
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
authors.forename: Hideshige
authors.initials: H
authors.lastname: Moriya
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002460:Cell Line; D002678:Chimera; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D021962:Membrane Microdomains; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011940:Receptor Aggregation; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018076:DNA, Complementary; D008565:Membrane Proteins; C487510:Nfam1 protein, mouse; D011956:Receptors, Cell Surface