
TCR ligand discrimination is enforced by competing ERK
2003年2月10日 · To evaluate a possible connection between ERK modification of receptor-bound Lck and SHP-1 binding, we examined the kinetics of ERK activation and the formation of p59 Lck associated with...
Lck Regulates the Threshold of Activation in Primary T Cells, While ...
The src family kinases p56lck (Lck) and p59fyn (Fyn) are the most proximal signaling molecules to be activated downstream of the T-cell receptor. Using an inducible transgenic model, we can regulate the expression of Lck in primary T cells and ask ...
细胞免疫研究的核心通路——T cell receptor signaling pathway( …
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 …
研究揭示T细胞受体信号激活的分子机制 - 知乎
2021年9月15日 · 研究认为,LCK Y394的反式自磷酸化是LCK激活的关键。 共受体分子如CD4/CD8被报道可以结合LCK(coreceptor-associated LCK),促进LCK激活。 然而,CD4/CD8的缺失并不阻碍T细胞的发育活化,只影响MHC特异性的T细胞识别,提示LCK的激活还存在其它调控形式。
ERK Activation in CAR T Cells Is Amplified by CD28-Mediated …
2020年4月24日 · Experimental measurements of ERK response in CAR-engineered T cells validate the model-generated hypothesis that CD28 activates ERK primarily through modifications of CD3ζ phosphorylation kinetics, likely as a result of increased recruitment of LCK. The model also generates additional hypotheses that can be used to guide new experiments.
Biophysical basis underlying dynamic Lck activation visualized by ...
We found that Lck kinase–dependent ERK activation responds faster to stimulation than ERK activation independent of Lck. Therefore, our data suggest that there are two signaling …
ERK Positive Feedback Regulates a Widespread Network of …
2013年7月17日 · Competing positive and negative signaling feedback pathways play a critical role in tuning the sensitivity of T cell receptor activation by creating an ultrasensitive, bistable switch to selectively enhance responses to foreign ligands while suppressing signals from self peptides.
T-cell receptor early signalling complex activation in response to ...
Lck is an essential component of the TCR ESC and signalling through ERK is blocked in its absence at the TCR. Previous studies in Jurkat cell lines have shown that Lck is also imperative for IFNα-induced ERK phosphorylation [2, 3].
The role of competing mechanisms on Lck regulation
2020年8月14日 · Erk-dependent phosphorylation of Ser 59 prevents the ability for Lck to interact with the inhibitory SHP-1, promoting a positive feedback mechanism of Lck regulation
LCK-Mediated RIPK3 Activation Controls Double-Positive
Mechanistically, lymphocyte-specific protein tyrosine kinase (LCK) activates RIPK3, which in turn leads to increases in the phosphatase activity of protein phosphatase 2 (PP2A), thereby suppressing hyper-activation of ERK in DP thymocytes.
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