JBC Transcription and Nuclear Factor Monoclonals

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J Biol Chem, Vol. 274, Issue 40, 28427-28435, October 1, 1999

Novel Isoform of Lymphoid Adaptor FYN-T-binding Protein (FYB-130) Interacts with SLP-76 and Up-regulates Interleukin 2 Production

Margaret VealeDagger §, Monika RaabDagger §, Zhuwen LiDagger §, Antonio J. da SilvaDagger §, Stine-Kathrein Kraeftparallel , Stanislawa Weremowicz**, Cynthia C. Morton**Dagger Dagger , and Christopher E. RuddDagger §§§

From the Departments of Dagger  Cancer Immunology and AIDS and parallel  Cancer Biology, Dana-Farber Cancer Institute and Departments of §§ Medicine and § Pathology, Harvard Medical School, Boston, Massachusetts 02115 and the Departments of ** Pathology and Dagger Dagger  Obstetrics and Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts 02115

T-cell activation involves the participation of protein-tyrosine kinases p56lck and ZAP-70/SYK as well as lymphoid proteins such as SLP-76 and FYB/SLAP. FYB/SLAP has the hallmarks of an adaptor protein that binds to the SH2 domains of the Src kinase FYN-T and SLP-76. Whereas two forms of FYB at 120 and 130 kDa have been identified biochemically, a cDNA encoding only the lower molecular weight isoform has been cloned (termed FYB-120 or SLAP-130). In this study, we report the isolation of an alternative isoform of FYB with a molecular mass of 130 kDa (FYB-130) that has the same structure as FYB-120 except for an insertion of 46 amino acids toward the carboxyl-terminal region of the protein. FYB-120 and FYB-130 share an ability to bind to the SH2 domains of FYN-T and SLP-76, to act as substrates for p59FYN-T, and to be expressed in the cytoplasm and nucleus of T-cells. Differences were noted between the isoforms in the efficiency of binding to SLP-76 and in the preferential expression of FYB-130 in mature T-cells. When co-expressed together with FYN-T and SLP-76, FYB-130 caused a significant increase in anti-CD3-driven NF-AT transcription. Finally, fluorescence in situ hybridization analysis localized the FYB gene to human chromosome 5 at position p13.1. FYB-130 therefore represents a novel variant of FYB protein that can up-regulate T-cell receptor-driven interleukin 2 production in mature T-cells.

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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