IRAK1 在 TLR7/8 或 9 刺激下招募 IKK 复合物
中文名称
通路描述
IRAK1 的激酶活性在 IL-1/TLR 诱导 NF-kappa-B 激活中的作用尚不明确。尽管激酶失活的 IRAK1 突变体仍能激活 NF-kappa-B,但 IRAK1 缺陷的 I1A 293 细胞经 LMP1(一种已知的 NF-kappa-B 激活物)刺激后,会出现 TRAF6 多聚泛素化和 IKKbeta 激活 [Song et al 2006]。另一方面,IRAK1 可增强 p65 Ser536 磷酸化 [Song et al 2006] 及 p65 与 NF-kappa-B 依赖靶基因启动子的结合 [Liu G et al 2008]。IRAK1 也被证明自身发生 Lys63 多聚泛素化(可能由 Pellino 蛋白介导,具有 E3 连接酶活性)。突变 IRAK1 上的泛素化位点可阻止其与 IKK 复合物的 NEMO 亚基相互作用,进而抑制 IL-1/TLR 诱导的 NF-kappa-B 激活 [Conze et al 2008]。这些数据表明,IRAK1 的激酶活性并非其激活 NF-kappa-B 所必需的,而其 Lys63 多聚泛素化则允许 IRAK1 与 NEMO 亚基结合,从而促进 TRAF6 和 TAK1 复合物与 IKK 复合物的结合,最终诱导 NF-kappa-B。
英文描述
Immunity to different classes of microorganisms is orchestrated by separate lineages of effector T helper (TH)-cells, which differentiate from naive CD4+ precursor cells in response to cues provided by antigen presenting cells (APC) and include T helper type 1 (Th1) and Th2. Th1 cells are characterized by the transcription factor T-bet and signal transducer and activator of transcription (STAT) 4, and the production of IFN-gamma. These cells stimulate strong cell-mediated immune responses, particularly against intracellular pathogens. On the other hand, transcription factors like GATA-3 and STAT6 drive the generation of Th2 cells that produce IL-4, IL-5 and IL-13 and are necessary for inducing the humoral response to combat parasitic helminths (type 2 immunity) and isotype switching to IgG1 and IgE. The balance between Th1/Th2 subsets determines the susceptibility to disease states, where the improper development of Th2 cells can lead to allergy, while an overactive Th1 response can lead to autoimmunity.
所含基因
93 个基因
CD247
CD3D
CD3E
CD3G
CD4
CHUK
DLL1
DLL3
DLL4
FOS
GATA3
HLA-DMA
HLA-DMB
HLA-DOA
HLA-DOB
HLA-DPA1
HLA-DPB1
HLA-DQA1
HLA-DQA2
HLA-DQB1
HLA-DQB2
HLA-DRA
HLA-DRB1
HLA-DRB3
HLA-DRB4
HLA-DRB5
IFNG
IFNGR1
IFNGR2
IKBKB
IKBKG
IL12A
IL12B
IL12RB1
IL12RB2
IL13
IL2
IL2RA
IL2RB
IL2RG
IL4
IL4R
IL5
JAG1
JAG2
JAK1
JAK2
JAK3
JUN
LAT
LCK
MAF
MAML1
MAML2
MAML3
MAPK1
MAPK10
MAPK11
MAPK12
MAPK13
MAPK14
MAPK3
MAPK8
MAPK9
NFATC1
NFATC2
NFATC3
NFKB1
NFKBIA
NFKBIB
NFKBIE
NOTCH1
NOTCH2
NOTCH3
PLCG1
PPP3CA
PPP3CB
PPP3CC
PPP3R1
PPP3R2
PRKCQ
RBPJ
RBPJL
RELA
RUNX3
STAT1
STAT4
STAT5A
STAT5B
STAT6
TBX21
TYK2
ZAP70