Raab M, Kang H, da Silva A, Zhu X, Rudd C E
Division of Tumor Immunology, Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Biol Chem. 1999 Jul 23;274(30):21170-9. doi: 10.1074/jbc.274.30.21170.
Protein-tyrosine kinases p56(Lck), SYK, and ZAP-70 and downstream adaptors LAT and SLP-76 have been implicated as essential components in T-cell activation. Another lymphoid-specific adaptor FYB/SLAP has also been identified as a predominant binding partner of SLP-76 and the Src kinase FYN-T, although its role in the activation process has been unclear. In this study, we demonstrate that FYN-T selectively phosphorylates FYB providing a template for the recruitment of FYN-T and SLP-76 SH2 domain binding. This interaction is unusual in its distinct cytoplasmic localization and its long term stable kinetics of phosphorylation. Furthermore, we demonstrate for the first time that the co-expression of all three components of the FYN-T-FYB-SLP-76 matrix can synergistically up-regulate T-cell receptor-driven interleukin 2 transcription activity. These findings document the existence of a T-cell receptor-regulated FYN-T-FYB pathway that interfaces with the adaptor SLP-76 and up-regulates lymphokine production in T-cells.
蛋白酪氨酸激酶p56(Lck)、SYK和ZAP-70以及下游衔接蛋白LAT和SLP-76被认为是T细胞活化的重要组成部分。另一种淋巴细胞特异性衔接蛋白FYB/SLAP也已被鉴定为SLP-76和Src激酶FYN-T的主要结合伴侣，尽管其在活化过程中的作用尚不清楚。在本研究中，我们证明FYN-T选择性地磷酸化FYB，为FYN-T和SLP-76 SH2结构域结合的募集提供了一个模板。这种相互作用在其独特的细胞质定位和其长期稳定的磷酸化动力学方面是不寻常的。此外，我们首次证明FYN-T-FYB-SLP-76基质的所有三个组分的共表达可以协同上调T细胞受体驱动的白细胞介素2转录活性。这些发现证明了存在一条与衔接蛋白SLP-76相互作用并上调T细胞中淋巴因子产生的T细胞受体调节的FYN-T-FYB途径。
