CD3和TCR zeta链的磷酸化
中文名称
通路描述
在T细胞受体（TCR）刺激之前，CD4/CD8关联的LCK保持与TCR分离，并由CSK维持其无活性状态。PAG结合的CSK磷酸化LCK的负调节酪氨酸残基，使LCK激酶结构域失活（步骤1）。CSK还通过结合抑制PTPN22，将其隔离从而抑制PTPN22（步骤2）。当TCR刺激时，CSK与PAG1（步骤3）和PTPN22（步骤4）解离，无法抑制LCK。此外，LCK通过PTPRC介导的负调节酪氨酸残基的去磷酸化而激活（步骤5）。CD4/CD8结合APC上的MHCII受体，并伴随LCK共定位于TCR。LCK通过其激活环上的酪氨酸残基发生自磷酸化而进一步激活（步骤6）。活性LCK进一步磷酸化CD3链上的酪氨酸残基。信号转导的CD3delta/epsilon/gamma和TCR zeta链包含一个关键的信号传导基序，称为免疫受体酪氨酸基激活基序（ITAM）。每个ITAM基序的两个关键酪氨酸残基由LCK磷酸化（步骤7）。
英文描述
CREB phosphorylation Nerve growth factor (NGF) activates multiple signalling pathways that mediate the phosphorylation of CREB at the critical regulatory site, serine 133. CREB phosphorylation at serine 133 is a crucial event in neurotrophin signalling, being mediated by ERK/RSK, ERK/MSK1 and p38/MAPKAPK2 pathways. Several kinases, such as MSK1, RSK1/2/3 (MAPKAPK1A/B/C), and MAPKAPK2, are able to directly phosphorylate CREB at S133. MSK1 is also able to activate ATF (Cyclic-AMP-dependent transcription factor). However, the NGF-induced CREB phosphorylation appears to correlate better with activation of MSK1 rather than RSK1/2/3, or MAPKAPK2. In retrograde signalling, activation of CREB occurs within 20 minutes after neurotrophin stimulation of distal axons.
所含基因
7 个基因