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TPL2 phosphorylates MEK1, SEK1
Stable Identifier
R-HSA-451649
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
Immune System (Homo sapiens)
Cytokine Signaling in Immune system (Homo sapiens)
Signaling by Interleukins (Homo sapiens)
Interleukin-1 family signaling (Homo sapiens)
Interleukin-1 signaling (Homo sapiens)
MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
Interleukin-17 signaling (Homo sapiens)
MAP kinase activation (Homo sapiens)
MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
Innate Immune System (Homo sapiens)
Toll-like Receptor Cascades (Homo sapiens)
Toll Like Receptor 10 (TLR10) Cascade (Homo sapiens)
MyD88 cascade initiated on plasma membrane (Homo sapiens)
MAP kinase activation (Homo sapiens)
MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
Toll Like Receptor 2 (TLR2) Cascade (Homo sapiens)
Toll Like Receptor TLR1:TLR2 Cascade (Homo sapiens)
MyD88:MAL(TIRAP) cascade initiated on plasma membrane (Homo sapiens)
MAP kinase activation (Homo sapiens)
MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
Toll Like Receptor TLR6:TLR2 Cascade (Homo sapiens)
MyD88:MAL(TIRAP) cascade initiated on plasma membrane (Homo sapiens)
MAP kinase activation (Homo sapiens)
MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
Toll Like Receptor 3 (TLR3) Cascade (Homo sapiens)
MAP kinase activation (Homo sapiens)
MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
Toll Like Receptor 4 (TLR4) Cascade (Homo sapiens)
MyD88-independent TLR4 cascade (Homo sapiens)
TRIF (TICAM1)-mediated TLR4 signaling (Homo sapiens)
MAP kinase activation (Homo sapiens)
MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
MyD88:MAL(TIRAP) cascade initiated on plasma membrane (Homo sapiens)
MAP kinase activation (Homo sapiens)
MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
Toll Like Receptor 5 (TLR5) Cascade (Homo sapiens)
MyD88 cascade initiated on plasma membrane (Homo sapiens)
MAP kinase activation (Homo sapiens)
MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
Toll Like Receptor 7/8 (TLR7/8) Cascade (Homo sapiens)
MyD88 dependent cascade initiated on endosome (Homo sapiens)
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation (Homo sapiens)
MAP kinase activation (Homo sapiens)
MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
Toll Like Receptor 9 (TLR9) Cascade (Homo sapiens)
MyD88 dependent cascade initiated on endosome (Homo sapiens)
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation (Homo sapiens)
MAP kinase activation (Homo sapiens)
MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
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The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Tpl2 (also known as Cot, officially known as MAP3K8) is constitutively bound to NFKB p105 (p105) which inhibits its MEK kinase activity in resting cells. Proteolysis of p105 frees Tpl2 from p105 and allows subsequent phosphorylation and activation of MEK1. Tpl2 can also activate SEK1 (MAP2K4). Phosphorylation of Tpl-2 is believed to play a role in its activation (Cho et al, 2005; Robinson et al. 2007).
Positions of phosphorylations represented here are inferred from general experimental data (Zheng & Guan, 1994).
Participants
Input
ATP [cytosol]
MAP2K1,MAP2K4 [cytosol]
(Homo sapiens)
Output
ADP [cytosol]
p-S218,S222-MAP2K1,p-S257,T261-MAP2K4 [cytosol]
(Homo sapiens)
Participates
as an event of
MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
Catalyst Activity
MAP kinase kinase kinase activity of p-S400,T290-MAP3K8 [cytosol]
Physical Entity
p-S400,T290-MAP3K8 [cytosol]
(Homo sapiens)
Activity
MAP kinase kinase kinase activity (GO:0004709)
Inferred From
Tpl2 phosphorylates Mek1, Sek1 (Mus musculus)
Authored
Ray, KP (2010-05-17)
Reviewed
Pinteaux, E (2010-05-17)
DeCicco-Skinner, KL (2015-08-21)
Created
Jupe, S (2010-01-07)
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