补体激活的凝集素通路
中文名称
通路描述
凝集素通路(LP)的激活由甘露糖结合凝集素(MBL)、CL-LK(由COLEC11和COLEC10形成)以及ficolins(FCN1、FCN2、FCN3)启动。它们都是Ca依赖的C型凝集素,在结合靶细胞表面的特定碳水化合物模式后启动补体级联反应。它们形成三聚体及更大的寡聚体。MBL和ficolins在血浆中以与MBL相关丝氨酸蛋白酶(MASP)同源二聚体复合物形式循环。MASP1、MASP2和MASP3均报道可介导补体激活。当人凝集素结合靶表面时,凝集素-MASP复合物发生构象变化,导致MASP切割和激活。活性MASP2切割C4生成C4a和C4b。C4b通过硫酯键结合靶细胞表面,然后结合循环的C2。结合的C2被MASP2切割产生C3转化酶C4b:C2a。活性MASP1被报道以类似MASP2的方式切割C2(Matsushita et al. 2000, Chen & Wallis 2004)。MASP1可切割前体MASP2,导致补体激活(Heja et al. 2012)。MASP1还可切割纤维蛋白原生成纤维蛋白肽B,并激活因子 XIII。MASP1可能具有去除'死C3'(C3(H2O))的作用(Hajela et al. 2002)。除了MASP1至3外,还有两种交替切割形式的MASP1(MAp44)和MASP2(sMAP)已涉及补体级联信号传导(Takahashi et al. 1999, Degn et al. 2010)。MASP3、sMAP和MAp44在凝集素通路中的功能尚待阐明。
英文描述
Synthesis of PIPs at the plasma membrane At the plasma membrane, subsequent phosphorylation of phosphatidylinositol 4-phosphate (PI4P) produces phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) while the actions of various other kinases and phosphatases produces phosphatidylinositol 3-phosphate (PI3P), phosphatidylinositol 5-phosphate (PI5P), phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2), and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) (Zhang et al. 1997, Gurung et al. 2003, Guo et al. 1999, Vanhaesebroeck et al. 1997, Tolias et al. 1998, Schaletzky et al. 2003, Kim et al. 2002, Clarke et al. 2010). Many of the phosphatidylinositol phosphatases that act at the plasma membrane belong to the myotubularin family. Enzymatically inactive myotubularin family members can heterodimerize with catalytically active mytotubularins to regulate their stability, activity and/or substrate specificity (Berger et al. 2006, Zou et al. 2012).
所含基因
53 个基因
ARF1
BMX
INPP4A
INPP4B
INPP5D
INPP5J
INPP5K
INPPL1
MTM1
MTMR1
MTMR14
MTMR2
MTMR3
MTMR6
MTMR8
MTMR9
OCRL
PI4K2A
PI4K2B
PIK3C2A
PIK3C2B
PIK3C2G
PIK3CA
PIK3CB
PIK3CD
PIK3CG
PIK3R1
PIK3R2
PIK3R3
PIK3R5
PIK3R6
PIP4K2A
PIP4K2B
PIP4K2C
PIP5K1A
PIP5K1B
PIP5K1C
PLEKHA1
PLEKHA2
PLEKHA3
PLEKHA4
PLEKHA5
PLEKHA6
PLEKHA8
PTEN
PTPN13
RAB14
RAB4A
RAB5A
RUFY1
SBF2
SYNJ1
SYNJ2