Frearson J A, Yi T, Alexander D R
Department of Immunology, The Babraham Institute, Cambridge, GB.
Eur J Immunol. 1996 Jul;26(7):1539-43. doi: 10.1002/eji.1830260720.
The role of cytosolic phosphotyrosine phosphatases (PTPase) in T cell receptor (TCR)-mediated signaling was investigated. PTPase activity was detected in a purified immunocomplex comprising aggregated TCR from the cell surface of Jurkat T cells. Since TCR aggregation results in phosphorylation of critical immunoreceptor tyrosine-based activation motifs (ITAM) in the TCR zeta chain, a doubly tyrosine-phosphorylated synthetic peptide containing the membrane-proximal zeta chain ITAM (zeta p ITAM) was used to characterize TCR zeta-associated PTPases. PTPase activity was detected in stable association with zeta p ITAM and the SH2 domain-containing PTPase PTP-1D (Syp, SH-PTP2) was identified in this complex. TCR stimulation resulted in increased total PTPase activity and PTP-1D protein in zeta p ITAM precipitates. TCR stimulation did not result in the tyrosine phosphorylation of PTP-1D but caused the rapid and transient tyrosine phosphorylation of a 110-120-kDa protein which associated selectively with the C-terminal SH2 domain of PTP-1D. This currently unidentified phosphotyrosine protein may be involved in localizing PTP-1D to the TCR following receptor stimulation.
研究了胞质磷酸酪氨酸磷酸酶（PTPase）在T细胞受体（TCR）介导的信号传导中的作用。在一个纯化的免疫复合物中检测到PTPase活性，该复合物包含来自Jurkat T细胞表面聚集的TCR。由于TCR聚集导致TCR ζ链中关键的基于免疫受体酪氨酸的激活基序（ITAM）磷酸化，因此使用含有膜近端ζ链ITAM（ζ p ITAM）的双酪氨酸磷酸化合成肽来表征与TCR ζ相关的PTPase。在与ζ p ITAM的稳定结合中检测到PTPase活性，并在该复合物中鉴定出含SH2结构域的PTPase PTP-1D（Syp，SH-PTP2）。TCR刺激导致ζ p ITAM沉淀物中的总PTPase活性和PTP-1D蛋白增加。TCR刺激不会导致PTP-1D的酪氨酸磷酸化，但会导致一种110-120 kDa蛋白的快速和短暂酪氨酸磷酸化，该蛋白选择性地与PTP-1D的C末端SH2结构域结合。这种目前尚未鉴定的磷酸酪氨酸蛋白可能参与受体刺激后将PTP-1D定位到TCR。
