UBCH8
UBE2L6
UniProt:O14933 UBE2L6
CDC2
CDC28A
CDK1
CDKN1
P34CDC2
UniProt:P06493 CDK1
PTPN2
PTPT
UniProt:P17706-2 PTPN2
PTP1B
PTPN1
UniProt:P18031 PTPN1
PRKACB
UniProt:P22694 PRKACB
HCP
PTP1C
PTPN6
UniProt:P29350 PTPN6
UBA7
UBE1L
UBE2
UniProt:P41226 UBA7
COT
ESTF
MAP3K8
UniProt:P41279 MAP3K8
ADAM17
CSVP
TACE
UniProt:P78536 ADAM17
PTP2C
PTPN11
SHPTP2
UniProt:Q06124 PTPN11
ISG43
USP18
UniProt:Q9UMW8 USP18
TAK1 phosphorylates MKK6
PIN1 mediated IRF3 degradation
p-RAF binds 14-3-3 beta/alpha
Transient dissociation of 14-3-3 upon Ras binding
Stabilisation of RAS:RAF by 14-3-3
Stabilisation of RAF by further phosphorylation
Phosphorylated human RAF1 binds to RAS:GTP complex
Activated RAF1 complex binds MEK
RAF1 phosphorylates MEK1
RAF1 phosphorylates MEK2
IFN alpha/beta binds to IFNAR2
Recruitment of IFNAR1
Activation of JAK kinases
Phosphorylation of INFAR1 by TYK2
Recruitment of STAT2 to p-IFNAR1
Phosphorylation of STAT2
Phosphorylation of STAT1
Release of p-STAT2:p-STAT1 dimer
Interaction of IRF9 with p-STAT2:p-STAT1
Translocation of ISGF3 complex to nucleus
Formation of p-STAT1 homodimer
Translocation of p-STAT1:p-STAT1 dimer to nucleus
ISGF3 binds the ISRE promoter elements in IFN-stimulated genes
Expression of IFN-induced genes
Inhibition of JAK kinase activity by SOCS1/3
UBP43 binds IFNAR2 and prevents JAK1 interaction
Dephosphorylation of TYK2 by PTP1B
Dephosphorylation of JAK1 by SHP1
Dephosphorylation of STAT1 by SHP2
Interaction of IFNG with IFNGR
Phosphorylation of JAK2
Transphosphorylation of JAK1
Phosphorylation of IFNGR1 by JAK kinases
Binding of STAT1 to p-IFNGR1
Phoshorylation of STAT1 by JAK kinases
Phosphorylation of STAT1 at Ser727
Release of STAT1 dimer from active receptor unit
Translocation of STAT1 dimer to nucleus
GAF binds the GAS promoter elements in the IFNG-regulated genes
Expression of IFNG-stimulated genes
SOCS-1 and SOCS-3 binds to p-JAK2
Dephosphorylation of JAKs by PTPs
PIAS1 binds p-STAT1 dimer
Dephosphorylation of p-STAT1 dimer by nuclear isoform of TCPTP
Activation of ISG15 by UBE1L E1 ligase
Transfer of ISG15 from E1 to E2 (UBCH8)
Interaction of E3 ligase with ISG15:E2 complex
ISGylation of host proteins
ISGylation of host protein filamin B
ISGylation of protein phosphatase 1 beta (PP2CB)
ISGylation of E2 conjugating enzymes
Interaction of ISG15 with NEDD4 and inhibition of Ebola virus budding
ISGylation of viral protein NS1
Translocation of Influenza A virus nonstructural protein 1 (NS1A) into the nucleus
ISGylation of IRF3
ISGylation of protein translation regulator 4EHP
Competitive inhibition of translation initiation by ISGylated 4EHP
Monoubiquitination of N-myristoyl GAG (P12493) protein
Regulation of protein ISGylation by ISG15 deconjugating enzyme USP18
Caspase-1 precursor is cleaved releasing p10 and p20 subunits
Formation of caspase-1 p10/p20 dimer
Caspase-1 active tetramer formation
Interleukin-1 family precursors are cleaved by caspase-1
Interleukin-1 family are secreted
Interleukin-1 receptor type 1 binds Interleukin 1
Interleukin-1 receptor type 2 binds Interleukin 1
IL1 receptor antagonist protein binds Interleukin 1 receptors
Interleukin-1 receptor type 1: Interleukin 1 binds Interleukin-1 receptor accessory protein, membrane associated isoform
IL1R1:IL1:IL1RAP binds MYD88 homodimer
IL1R1:IL1:IL1RAP:MYD88 homodimer binds IRAK4
The Interleukin 1 receptor complex binds Tollip
IRAK4 is activated by autophosphorylation
IRAK1 binds to MYD88 within the IL1R complex
IRAK4 phosphorylates IRAK1
IRAK4-activated IRAK1 autophosphorylates
IRAK2 is phosphorylated downstream of IRAK4 following IL1 receptor activation
Hyperphosphorylated IRAK1 associates with TRAF6
p62:MEKK3 binds to TRAF6
TRAF6 binding leads to IRAK1:TRAF6 release
IRAK1 induces oligomerisation of TRAF6
TRAF6 auto-ubiquitinates with Lys63-linked polyubiquitin chains
Polyubiquitinated TRAF6 interacts with TAK1 complex
TAK1 is activated within the TAK1 complex
IRAK1 and 4 interact with Pellino1,2 and 3
IRAK1 and 4 can phosphorylate Pellino-1 and 2.
Pellino ubiquitinates IRAK1
NEMO binds polyubiquitinated IRAK1
The IKKB complex phosphorylates NFkB p105
The SCF betaTrCP complex binds p-NFkB p105
Beta-TrCP ubiquitinates then dissociates from p-NFKB p105
NFKB p105, TPL2 (COT) and ABIN2 form a stable complex
TPL2 phosphorylates MEK1, SEK1
IL2RB associates with JAK1
IL2RG associates with JAK3
Interleukin-2 receptor alpha binds interleukin-2
Interleukin-2 receptor alpha:IL2 binds Interleukin-2 receptor beta
Interleukin-2: IL2 receptor alpha:beta binds IL2 receptor gamma subunit
Within the IL-2R complex JAK3 phosphorylates JAK1
JAK1 phosphorylates Y338, Y392 and Y510 of IL2RB
Phosphorylation of IL2RB Y338 enables SHC recruitment
Phosphorylation of IL2RB Y338, Y392 or Y510 enables STAT recruitment
SHC1 bound to IL2 receptor is phosphorylated
Phosphorylated SHC1 recruits GRB2:GAB2
SHC1 mediates cytokine-induced phosphorylation of GAB2
Gab2 binds the p85 subunit of Class 1A PI3 kinases
Phosphorylated SHC recruits GRB2:SOS1
SOS1 activates H-Ras
Phosphorylated SHC1 recruits SHIP
The SHC1:SHIP1 complex is stabilized by GRB2
Recruited STAT5 is phosphorylated
Phosphorylated STAT5 is released
Phosphorylated STAT5 forms dimers
STAT5 dimers translocate to the nucleus and bind to specific DNA sequences
Syk binds IL2RB
SYK is a substrate for JAK1
Pyk2 associates with Jak3
Pyk2 is activated following IL2 stimulation
The common beta chain IL3RB binds JAK2
GM-CSF receptor alpha subunit binds GM-CSF
GM-CSF receptor alpha:GM-CSF binds Bc
Interleukin-5 is a homodimer
Interleukin-5 receptor alpha subunit binds Interleukin-5
Interleukin-5:Interleukin-5 receptor alpha binds IL3RB:JAK2
Interleukin-3 receptor alpha subunit binds Interleukin-3
Interleukin-3 receptor alpha: Interleukin-3 binds IL3RB:JAK2
The receptor is activated
JAK2 is phosphorylated, activated
STAT5 is recruited by JAK2
Activation of STAT5a/b by JAK2
p-STAT5 is released from the receptor complex
Tyrosine kinases phosphorylate the receptor
Recruitment of SHC1 is mediated by Y593 of the common beta chain
SHC1 bound to the common beta chain becomes tyrosine phosphorylated
CBL, GRB2, FYN and PI3K p85 subunit are constitutively associated
CBL is tyrosine phosphorylated
CBL ubiquitinates PI3K
CBL binds CRK
CBL:CRKL binds RAPGEF1
CBL binds B-cell linker protein
CBL binds VAV
IL3 stimulation induces Vav binding to Tec kinase
SHP1 and SHP2 bind the common beta chain
SHP1 and SHP2 dephosphorylate Y628 of IL3RB
SHP2 can recruit GRB2
IL3RB is phosphorylated on Ser-585
p-S585-IL3RB binds 14-3-3 proteins
14-3-3 zeta binding allows recruitment of PI3K
JAKs associate with IL6RB (gp130)
Interleukin-6 binds to soluble IL-6 receptor
IL6:sIL6R binds sgp130
Interleukin-6 binds to IL-6 receptor alpha subunit
IL6:sIL6R binds to JAKs:IL6RB (gp130)
IL6:IL6RA binds JAKs:IL6RB (gp130)
Assembly of a hexameric IL-6 receptor
JAK activation
Phosphorylation of gp130
STATs bind gp130 phosphotyrosines
Tyrosine phosphorylation of STATs by IL6 receptor
Serine phosphorylation of STATs
Phosphorylated STATs are released
Phosphorylated STAT1, STAT3 form dimers
STAT1/3 dimers translocate to the nucleus
SHP2 binds gp130 phosphotyrosine-759
SHP2 is phosphorylated
SOCS3 binds gp130
SHP2 binds c-Cbl upon IL-6 stimulation
PPBSF is a complex of IL7 and HGFbeta
IL7RA associates with JAK1
Interleukin-7 binds IL7RA:JAK1
Interleukin-7:IL7RA:JAK1 binds Gc:JAK3
IL7RA is phosphorylated on Y449
p(Y449)-IL7RA mediates STAT5 activation
p85 binds p(Y449)-IL7RA
Growth hormone forms dimers and oligomers
Growth hormone receptor binds JAK2
Growth hormone receptor dimerizes
Growth hormone binds the growth hormone receptor
GH:GHR:JAK2 complex undergoes a conformational change
JAK2 phosphorylation
JAK2 phosphorylation of IRS-1/2
JAK2 phosphorylation of GHR
STAT5 association with GHR
STAT5 tyrosine phosphorylation
Growth hormone receptor binds Lyn
Lyn activates ERK
JAK2 binds STAT1/3
JAK2 phosphorylates STAT1/STAT3
SOCS binding to GHR
SOCS binding to JAK2
PTP1B binds the GH receptor complex
PTP1B dephosphorylates GHR
PTP1B dephosphorylates JAK2
SHP1 (PTPN6) binds JAK2 in the receptor complex
SHP1 (PTPN6) dephosphorylates JAK2
Metalloprotease cleavage of GHR
GHBP binds GH
GHBP binds GHR
GHR internalization
PRLR associates with JAK2
PRLR:JAK2 dimerizes
Prolactin receptor ligands bind the prolactin receptor
PRLR activation
SH2B binds JAK2
Tyrosine phosphorylation of PRLR
PRLR binds STAT5
PRLR-bound STAT5 is phosphorylated
PRLR binds SHP2 (PTPN11)
PRLR is phosphorylated at Ser-349
PRLR binds SCF beta-TrCP complex
Prolactin receptor is internalized
Activated TAK1 mediates phosphorylation of the IKK Complex
Inactivation of MEK1 by p34cdc2
MEK1 binds ERK-1
MEK1 phosphorylates ERK-1
Dissociation of phospho-ERK-1:MEK1
Dimerisation of phospho-ERK-1
Nuclear translocation of phospho-ERK-1 dimer
MEK2 binds ERK-2
MEK2 phosphorylates ERK-2
Dissociation of phospho-ERK-2:MEK2
Dimerisation of phospho-ERK-2
Nuclear translocation of phospho-ERK-2 dimer
ERK activation
ERK1 activation
ERK2 activation
RAF/MAP kinase cascade
RAF activation
MEK activation
RAF phosphorylates MEK
Cytokine Signaling in Immune system
Interferon Signaling
Interferon alpha/beta signaling
Regulation of IFNA signaling
Interferon gamma signaling
Regulation of IFNG signaling
Antiviral mechanism by IFN-stimulated genes
ISG15 antiviral mechanism
Signaling by Interleukins
Interleukin-1 processing
Interleukin-1 signaling
Interleukin-2 signaling
Interleukin receptor SHC signaling
Interleukin-3, 5 and GM-CSF signaling
Regulation of signaling by CBL
Interleukin-6 signaling
Interleukin-7 signaling
Growth hormone receptor signaling
Prolactin receptor signaling