GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate nuclear factor of activated T cell activation.
GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate nuclear factor of activated T cell activation.
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DOI：
10.1084/jem.189.8.1243
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发表时间：
1999-04-19
期刊：
影响因子：
--
通讯作者：
Clark EA
中科院分区：
文献类型：
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作者：
Law CL;Ewings MK;Chaudhary PM;Solow SA;Yun TJ;Marshall AJ;Hood L;Clark EA
T 细胞抗原受体 (TCR) 信号的传播涉及许多接头分子。含SH2结构域的蛋白76（SLP-76）与鸟嘌呤核苷酸交换因子Vav相互作用，激活活化细胞核因子（NF-AT），其表达是正常T细胞发育所必需的。我们报告了一种新型 Grb2 样接头分子的克隆和表征，该接头分子被命名为淋巴系统 Grb2 相关蛋白 (GrpL)。 GrpL 的表达仅限于造血组织，它与 Grb2 的区别在于具有富含脯氨酸的区域。 GrpL 可以与 SLP-76 共免疫沉淀，但不能与 Jurkat 细胞裂解物中的 Sos1 或 Sos2 共沉淀。相比之下，Grb2 可以与 Sos1 和 Sos2 共免疫沉淀，但不能与 SLP-76 共沉淀。此外，由抗CD3刺激的T细胞制备的去污剂裂解物中酪氨酸磷酸化的LAT/pp36/38与Grb2相关，但与GrpL无关。这些数据揭示了 T 细胞中存在涉及 GrpL 和 Grb2 的不同复合物。 GrpL-SLP-76 复合物的功能作用表明 GrpL 能够单独发挥作用或与 SLP-76 协同作用以增强 Jurkat T 细胞中 NF-AT 的激活。
Propagation of signals from the T cell antigen receptor (TCR) involves a number of adaptor molecules. SH2 domain–containing protein 76 (SLP-76) interacts with the guanine nucleotide exchange factor Vav to activate the nuclear factor of activated cells (NF-AT), and its expression is required for normal T cell development. We report the cloning and characterization of a novel Grb2-like adaptor molecule designated as Grb2-related protein of the lymphoid system (GrpL). Expression of GrpL is restricted to hematopoietic tissues, and it is distinguished from Grb2 by having a proline-rich region. GrpL can be coimmunoprecipitated with SLP-76 but not with Sos1 or Sos2 from Jurkat cell lysates. In contrast, Grb2 can be coimmunoprecipitated with Sos1 and Sos2 but not with SLP-76. Moreover, tyrosine-phosphorylated LAT/pp36/38 in detergent lysates prepared from anti-CD3 stimulated T cells associated with Grb2 but not GrpL. These data reveal the presence of distinct complexes involving GrpL and Grb2 in T cells. A functional role of the GrpL–SLP-76 complex is suggested by the ability of GrpL to act alone or in concert with SLP-76 to augment NF-AT activation in Jurkat T cells.