NMDA受体介导的神经元传递的负调节
中文名称
通路描述
NMDA受体介导的神经元传递的持续时间可通过激活的钙调蛋白与激活的NMDA受体结合而受限。除了缩短NMDA通道孔开放状态外，钙调蛋白还干扰ACTN2介导的NMDA受体与突触后密度（Ehlers et al. 1996, Wyszynski et al. 1997）的锚定。蛋白磷酸酶PPM1E和PPM1F去磷酸化激活的钙/钙调蛋白依赖性激酶（CaMKs），从而阻止CaMK介导的信号转导（Ishida, Okuno et al. 1998, Ishida et al. 1998, Kitani et al. 2003）。
英文描述
Phosphorylation of CD3 and TCR zeta chains Prior to T cell receptor (TCR) stimulation, CD4/CD8 associated LCK remains seperated from the TCR and is maintained in an inactive state by the action of CSK. PAG bound CSK phosphorylates the negative regulatory tyrosine of LCK and inactivates the LCK kinase domain (step 1). CSK also inhibits PTPN22 by sequestering it via binding (step 2). Upon TCR stimulation, CSK dissociates from PAG1 (step 3) and PTPN22 (step4) and is unable to inhibit LCK. Furthermore, LCK becomes activated via PTPRC-mediated dephosphorylation of negative regulatory tyrosine residues (step 5). CD4/CD8 binds MHCII receptor in APC and the associated LCK co-localizes with the TCR. LCK is further activated by trans-autophosphorylation on the tyrosine residue on its activation loop (step 6). Active LCK further phosphorylates the tyrosine residues on CD3 chains. The signal-transducing CD3 delta/epsilon/gamma and TCR zeta chains contain a critical signaling motif known as the immunoreceptor tyrosine-based activation motif (ITAM). The two critical tyrosines of each ITAM motif are phosphorylated by LCK (step 7).
所含基因
16 个基因