在T细胞中，首先磷酸化CD3 ITAM的激酶是Lck。 Lck的N端有一个SH4结构域，常被脂肪酸化修饰而能够固定在细胞膜内侧，另外在N端也有两个Cys残基，通过结合锌离子和CD4或CD8的胞内尾巴相互作用。

蛋白激酶Lck可以将胞外抗原识别输入转换为TCR磷酸化信号输出，即Lck可以磷酸化免疫受体酪氨酸激活模体ITAMs中的 酪氨酸残基，进而招募效应激酶Zap70，并将Zap70磷酸化激活，从而引起下游Lat等调控因子执行T细胞应答反应。

Phosphatases and the Csk kinase control Lck activity: phosphatases can open and inactivate the structure, while Csk can only close it. The activation and modifications of Lck differ between normal and pathological conditions, such as cancer, …

2022年11月14日 · Here we show that the conserved oncogenic tyrosine kinase Activated CDC42 kinase 1 (ACK1) is able to phosphorylate CSK at Tyrosine 18 (pY18), which enhances CSK function, constraining T-cell ...

Subsequent peptide binding studies revealed that Csk can bind to a peptide corresponding to the Lck-autophosphorylation site only when it is phosphorylated. These findings suggest that autophosphorylation of Lck at Tyr394 triggers an interaction with Csk and thereby facilitates subsequent phosphorylation and inactivation of Lck.

2024年11月7日 · Gao and Skolnick use deep learning to identify protein-protein interaction partners of tyrosine kinase Lck among ∼1,000 immune-related proteins. Predicted structures for several complexes reveal potential molecular mechanisms, providing insights into their functions in T cell regulation and signaling.

2020年8月14日 · Csk is a kinase that phosphorylates the inhibitory Tyr 505 resulting in the inactivation of Lck and acts in direct opposition to the activity of CD45. The role of Csk in regulating Lck and subsequent downstream signaling …

2017年10月30日 · Phosphorylation of Y505 is catalyzed by C-terminal SRC kinase (CSK) 8, 9 and antagonized primarily by the membrane-bound tyrosine phosphatase CD45 (ref. 10). This modification can regulate...

2016年6月8日 · In the immune system, cAMP is a potent negative regulator of T cell receptor-mediated activation of effector T cells (Teff) acting through a proximal PKA/Csk/Lck pathway anchored via a scaffold consisting of the AKAP Ezrin holding PKA, the linker protein EBP50, and the anchoring protein phosphoprotein associated with glycosphingolipid-enriched ...

2004年10月18日 · CD45 and Csk provide positive and negative regulatory control of SFK functions, respectively, and Csk is constitutively bound to the transmembrane adapter protein, PAG/Cbp.