Interleukin-17 signaling (Homo sapiens)
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Description
Interleukin-17 (IL17) is a family of cytokines (Kawaguchi et al. 2004, Gu et al. 2013). IL17A, the founding member of the family is able to induce the production of other cytokines and chemokines, such as IL6, IL8, and granulocyte colony-stimulating factor (G-CSF) in a variety of cell types, including activated T-cells. It plays a pivotal role in host defenses in response to microbial infection and is involved in the pathogenesis of autoimmune diseases and allergic syndromes. IL17 activates several downstream signaling pathways including NFkB, MAPKs and C/EBPs, inducing the expression of antibacterial peptides, proinflammatory chemokines and cytokines and matrix metalloproteases (MMPs). IL17 can stabilize the mRNA of genes induced by TNF-alpha. IL17 signal transduction is mediated by the cytosolic adaptor molecule ACT1 (also known as CIKS).
The receptor for IL17D is unknown (Gu et al. 2013). View original pathway at:Reactome.
The receptor for IL17D is unknown (Gu et al. 2013). View original pathway at:Reactome.
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dimer,L17F
dimer,IL17A:IL17FThere are three major groups of MAP kinases
ERK1 and ERK2 are activated in response to growth stimuli. Both JNKs and p38-MAPK are activated in response to a variety of cellular and environmental stresses. The MAP kinases are activated by dual phosphorylation of Thr and Tyr within the tripeptide motif Thr-Xaa-Tyr. The sequence of this tripeptide motif is different in each group of MAP kinases: ERK (Thr-Glu-Tyr); p38 (Thr-Gly-Tyr); and JNK (Thr-Pro-Tyr).
MAPK activation is mediated by signal transduction in the conserved three-tiered kinase cascade: MAPKKKK (MAP4K or MKKKK or MAPKKK Kinase) activates the MAPKKK. The MAPKKKs then phosphorylates a dual-specificity protein kinase MAPKK, which in turn phosphorylates the MAPK.
The dual specificity MAP kinase kinases (MAPKK or MKK) differ for each group of MAPK. The ERK MAP kinases are activated by the MKK1 and MKK2; the p38 MAP kinases are activated by MKK3, MKK4, and MKK6; and the JNK pathway is activated by MKK4 and MKK7. The ability of MAP kinase kinases (MKKs, or MEKs) to recognize their cognate MAPKs is facilitated by a short docking motif (the D-site) in the MKK N-terminus, which binds to a complementary region on the MAPK. MAPKs then recognize many of their targets using the same strategy, because many MAPK substrates also contain D-sites.
The upstream signaling events in the TLR cascade that initiate and mediate the ERK signaling pathway remain unclear.
Annotated Interactions
dimer,L17F
dimer,IL17A:IL17FInterleukin-25 (IL25, IL17E) dimers bind a receptor complex of Interleukin-17 receptor B (IL17RB) and Interleukin-17 receptor A (IL17RA) (Rickel et al. 2008). This is a Black Box event because the order of receptor binding is unclear.