NFAM1, an immunoreceptor tyrosine-based activation motif-bearing molecule that regulates B cell development and signaling

Makoto Ohtsuka, Hisashi Arase, Arata Takeuchi, Sho Yamasaki, Ritsuko Shiina, Tadahiro Suenaga, Daiju Sakurai, Tadashi Yokosuka, Noriko Arase, Makio Iwashima, Toshio Kitamura, Hideshige Moriya, Takashi Saito

Research output: Contribution to journalArticlepeer-review

79 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8126-8131
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number21
DOIs
Publication statusPublished - May 21 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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