Signal pathways of IL-17. The IL-17R complex is composed of two IL-17RA and
one IL-17RC; both subunits encode SEFIR domains. After activation, the
intracellular IL-17 signaling includes ACT1-dependent and -independent
downstream pathways. Left: the ACT1-dependent pathway: IL-17RA engages its
SEFIR domain to recruit the adaptor protein ACT1. ACT1 contains a
TRAF6-binding motif and can bind TRAF6, TRAF3 and TAK1, which subsequently
leads to activation of the canonical NF-κB pathway. ACT1 is also
required for the activation of MAPK p38, and this pathway leads to the
stabilization of mRNAs, particularly those encoding chemokines and
cytokines. Right: the ACT1-independent pathway involves JAK1 and PI3K,
followed by subsequent inactivation of GSK-3β. Both ACT1-dependent and
-independent pathways contribute to the activation of transcription factors
C/EBP-β and C/EBP-δ. ACT1, nuclear factor-κB activator 1; C/EBP,
CCAAT/enhancer-binding protein; GSK-3β, glycogen synthase kinase-3β
JAK1, Janus kinase 1; MAPK, mitogen-activated protein kinase; NF-κB,
nuclear factor-κB; PI3K, phosphatidylinositol 3-kinase; SEFIR,
SEF/IL-17R; TAK1, TGF-β-activated kinase 1; TRAF6, tumor-necrosis factor
receptor-associated factor 6.