Cloning of a novel T-cell protein FYB that binds FYN and SH2-domain-containing leukocyte protein 76 and modulates interleukin 2 production
Cloning of a novel T-cell protein FYB that binds FYN and SH2-domain-containing leukocyte protein 76 and modulates interleukin 2 production
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DOI：
10.1073/pnas.94.14.7493
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发表时间：
1997-07-08
影响因子：
11.1
通讯作者：
Rudd, CE
中科院分区：
文献类型：
--
作者：
DaSilva, AJ;Li, ZW;Rudd, CE
T 细胞受体 zeta (TcR zeta)/CD3 连接启动涉及 src 激酶 p56(lck) 和 zeta 相关蛋白 70 的信号级联，导致 TcR zeta、Vav、含 SH2 结构域的白细胞蛋白 76 (SLP-76)、cbl 和 p120/130 等底物磷酸化。 FYN 结合蛋白（FYB 或 p120/130）与 TcR zeta/CD3 复合物 p59(fyn) 结合，并响应受体连接而发生酪氨酸磷酸化。在这项研究中，我们报道了人和鼠FYB的cDNA克隆，并表明它的表达仅限于T细胞和骨髓细胞，并具有整体独特的亲水序列，其中包括几个基于酪氨酸的基序、基于脯氨酸的I型和II型SH3结构域结合基序、几个假定的富含赖氨酸/谷氨酸的核定位基序和SH3样结构域。除了结合 src 激酶 p59(fyn) 外，FYB 还特异性结合造血信号蛋白 SLP-76，这是由 SLP-76 SH2 结构域介导的相互作用。与此相一致的是，响应 TcR zeta/CD3 连接，FYB 的表达增强了 T 细胞杂交瘤 DC27.10 的白细胞介素 2 分泌。因此，FYB 是一种新型造血蛋白，作为 T 细胞中 FYN 和 SLP-76 信号级联的组成部分。
T cell receptor zeta (TcR zeta)/CD3 ligation initiates a signaling cascade that involves src kinases p56(lck) and zeta-associated protein 70, leading to the phosphorylation of substrates such as TcR zeta, Vav, SH2-domain-containing leukocyte protein 76 (SLP-76), cbl, and p120/130. FYN binding protein (FYB or p120/130) associates with p59(fyn), the TcR zeta/CD3 complex, and becomes tyrosine-phosphorylated in response to receptor ligation. In this study, we report the cDNA cloning of human and murine FYB and show that it is restricted in expression to T cells and myeloid cells and possesses an overall unique hydrophilic sequence with several tyrosine-based motifs, proline-based type I and type II SH3 domain binding motifs, several putative lysine/glutamic acid-rich nuclear localization motifs, and a SH3-like domain. In addition to binding the src kinase p59(fyn), FYB binds specifically to the hematopoietic signaling protein SLP-76, an interaction mediated by the SLP-76 SH2 domain. In keeping with this, expression of FYB augmented interleukin 2 secretion from a T cell hybridoma, DC27.10, in response to TcR zeta/CD3 ligation. FYB is therefore a novel hematopoietic protein that acts as a component of the FYN and SLP-76 signaling cascades in T cells.