NFAM1, an immunoreceptor tyrosine-based activation motif-bearing molecule that regulates B cell development and signaling.
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.
Ohtsuka
Makoto
M
Department of Molecular Genetics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Arase
Hisashi
H
Takeuchi
Arata
A
Yamasaki
Sho
S
Shiina
Ritsuko
R
Suenaga
Tadahiro
T
Sakurai
Daiju
D
Yokosuka
Tadashi
T
Arase
Noriko
N
Iwashima
Makio
M
Kitamura
Toshio
T
Moriya
Hideshige
H
Saito
Takashi
T
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
D018076:DNA, Complementary; D008565:Membrane Proteins; C487510:Nfam1 protein, mouse; D011956:Receptors, Cell Surface