Monika Raab

Journal - Journal of Biological Chemistry

Abstract :

From the  Division of Tumor Immunology, Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute and Departments of § Medicine and ¶ Pathology, Harvard Medical School, Boston, Massachusetts 02115 Protein-tyrosine kinases p56Lck, SYK, and ZAP-70 and downstream adaptors LAT and SLP-76 have been implicated as essential componentsin T-cell activation. Another lymphoid-specific adaptor FYB/SLAPhas also been identified as a predominant binding partner of SLP-76and the Src kinase FYN-T, although its role in the activationprocess has been unclear. In this study, we demonstrate that FYN-Tselectively phosphorylates FYB providing a template for the recruitmentof FYN-T and SLP-76 SH2 domain binding. This interaction is unusualin its distinct cytoplasmic localization and its long term stablekinetics of phosphorylation. Furthermore, we demonstrate for thefirst time that the co-expression of all three components of theFYN-T-FYB-SLP-76 matrix can synergistically up-regulate T-cellreceptor-driven interleukin 2 transcription activity. These findingsdocument the existence of a T-cell receptor-regulated FYN-T-FYBpathway that interfaces with the adaptor SLP-76 and up-regulateslymphokine production in T-cells. Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.Protein-tyrosine kinases p56Lck, SYK, and ZAP-70 and downstream adaptors LAT and SLP-76 have been implicated as essential componentsin T-cell activation. Another lymphoid-specific adaptor FYB/SLAPhas also been identified as a predominant binding partner of SLP-76and the Src kinase FYN-T, although its role in the activationprocess has been unclear. In this study, we demonstrate that FYN-Tselectively phosphorylates FYB providing a template for the recruitmentof FYN-T and SLP-76 SH2 domain binding. This interaction is unusualin its distinct cytoplasmic localization and its long term stablekinetics of phosphorylation. Furthermore, we demonstrate for thefirst time that the co-expression of all three components of theFYN-T-FYB-SLP-76 matrix can synergistically up-regulate T-cellreceptor-driven interleukin 2 transcription activity. These findingsdocument the existence of a T-cell receptor-regulated FYN-T-FYBpathway that interfaces with the adaptor SLP-76 and up-regulateslymphokine production in T-cells.