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IL-17 Signaling Pathway

The IL-17 family consists of six members IL-17A-F, while the IL-17 receptor family consists of five members IL-17RA to IL-17RE. IL-17RA is a common receptor that forms heterodimeric complexes with IL-17RB, IL-17RC, and IL-17RE. Thus far, all of the IL-17 receptors recruit Act1 as an adaptor molecule for downstream signaling. IL-17A and IL-17F signals through the IL-17RA-RC complex, triggering TRAF6-dependent target gene transcription and TRAF6-independent IKKi-dependent mRNA stabilization, both of which are important for host defense and contributes to the pathogenesis of autoimmune diseases and cancer. IL-17 signaling is tightly controlled at different levels of the signaling cascade. At the receptor level, IL-17RD interacts with Act1 basally, sequestering it from IL-17RA and TRAF6 until IL-17 stimulation. TRAFs like TRAF3 and TRAF4 act to disrupt downstream signaling complex formation. While TRAF3 binds to the IL-17R to prevent the recruitment of Act1 and TRAF6, TRAF4 competes with TRAF6 for Act1 binding. Deubiquitinating enzymes like USP25 and A20 regulate the ubiquitination status of TRAFs (like TRAF5 and TRAF6), placing a brake on the signaling cascade. The IL-17A-dependent micro-RNA, miR-23b, regulates NFκB activation. IL-17A-induced transcription factors such as C/EBPδ inhibits inflammatory gene expression. IL-17E (IL-25) signaling through the IL-17RA-RB receptor complex induces Th2 responses by activating MAPK and NFκB pathways. IL-17C signals through the IL-17RA-RE complex. IL-17B have been shown to interact with IL-17RB. The receptor for IL-17D is unknown. The biological function of IL-17B, IL-17C and IL-17D are as yet elusive.

IL17B IL17A IL17F IL17A/F IL17D IL17A IL17C IL17 IL17RB IL17RA IL17RC IL17RA IL17RB IL17RA IL17RE ACT1 ACT1 ACT1 HSP90 HSP90 TBK1 TRADD FADD Caspase TRAF2 TRAF5 TRAF3 TRAF4 TRAF6 MAP3K7 ERK1/3 GSK3B CEBPB CEBPB CEBPD CEBP p38 MKK JNK AP-1 IKK ELAVL1 USP25 IkB IkB NF-kB Chemokines Tissue remodeling Cytokines mRNA stability SRSF1 TAB1/2 MAP3K7 TRAF6 Apoptosis

IL-17 Signaling Pathway from A to Z

ACT1 search result
AP-1 search result
CEBP search result
CEBPB search result
CEBPD search result
ELAVL1 search result
ERK1/3 search result
FADD search result
GSK3B search result
HSP90 search result
IkB search result
IKK search result
IL17A search result; Category: IL17A
IL17A/F search result; Category: IL17A/F
IL17B search result; Category: IL17B
IL17C search result; Category: IL17C
IL17D search result; Category: IL17D
IL17E search result; Category: IL17E
IL17F search result; Category: IL17F
IL17RA search result; Category: IL17RA
IL17RB search result; Category: IL17RB
IL17RC search result; Category: IL17RC
IL17RE search result
JNK search result
MAP3K7 search result
MKK search result
NF-kB search result
p38 search result
SRSF1 search result
TAB1/2 search result
TBK1 search result
TRADD search result
TRAF2 search result
TRAF3 search result
TRAF4 search result
TRAF5 search result
TRAF6 search result
IL17 search result; Category: IL17
Caspase search result
USP25 search result
Chemokines search result
Cytokines search result
Tissue remodeling search result
mRNA stability search result
Apoptosis search result

Thanks to Sino Biological for providing the pathways.