We propose a two-step model for CD28 activation in which the initial recruitment of Lck to CD28 is mediated by clusters of basic residues. Subsequent binding of the Lck SH2 domain to the phosphorylated PYAP motif of CD28 then stabilizes the open, active conformation of Lck and facilitates its phosphorylation of recruited PKCθ.

2022年7月11日 · 酪氨酸激酶LCK是TCR通路的一个关键调节结点，LCK的构象以及细胞定位变化将影响TCR信号传导。 LCK的活性调节受其两个酪氨酸残基磷酸化的影响：位于催化结构域活化环的Y394位点磷酸化对LCK活性是正调节，而位于羧基末端的Y505位点的磷酸化则对蛋白活性有负调节作用。 不同磷酸酶和激酶对着两个位点磷酸化修饰的调节，可以影响LCK的构象和活性（图1）。 （1）Y505位点磷酸化以及非活性/初始构象的转化. 酪氨酸激酶GSK对Y505的磷酸化修 …

In this study we show that CD28, but not CD4, engagement induces Lck recruitment into lipid rafts and accumulation of the kinase at IS, by a mechanism dependent on Vav-1 and requiring the CD28 binding motif for Lck.

Our results show that CD28 co-stimulation specifically accelerated recruitment of ZAP70 to the TCRζ chain in MCs and increased ZAP70 activation. CD28-mediated acceleration of ZAP70 recruitment was driven by enhanced Lck recruitment to the MCs.

2005年4月1日 · In our recent paper titled “CD28 and Lipid Rafts Coordinate Recruitment of Lck to the Immunological Synapse of Human T Lymphocytes,” we demonstrated the essential role of the C-terminal 208 PXXPP 212 motif in CD28 for the recruitment of lipid rafts, and therefore of the raft-associated protein Lck, to the immunological synapse (IS) . We do ...

2002年2月4日 · CD4 recruited Lck to the T cell–APC interface, whereas CD28 sustained Lck activation. These data show how the multiple interactions afforded by the immunological synapse drive efficient and...

2024年12月24日 · CD28-mediated acceleration of ZAP70 recruitment was driven by enhanced Lck recruitment to the MCs. A greater spatial separation between active and inactive species of Lck was also observed in the MCs as a consequence of CD28 co-stimulation.

2 天之前 · 激活的TCR触发信号体的组装，主要成分包括酪氨酸激酶（如Lck和Zap70）、骨架（如Lat、SLP76和Themis）以及磷脂酶Cγ1（PLC γ1），另外也包括酪氨酸磷酸酶和E3泛素连接酶，如SHP1如Cbl。 T细胞第二个激活信号由 CD28 等共刺激受体提供。CD28增强TCR驱动的酪氨 …

2017年3月9日 · Lck, the kinase that phosphorylates TCR, CD28, and PD-1, was the second-best target for PD-1–bound Shp2 in the reconstitution system. Both the activating (Y394) and inhibitory (Y505) tyrosines were ~50% dephosphorylated at similar levels of …

CD28 inhibits Rap1 activation because it selectively stimulates an extrinsic Rap1 GTPase activity. The ability of CD28 to stimulate Rap1 GTPase activity was dependent on the tyrosine kinase Lck. Our results suggest that CD28-mediated Rap1 GTPase-activating protein activation can help explain the augmentation of ERKs during CD28 costimulation.