CDC2
label: CDC28A
label: CDK1
label: CDKN1
label: P34CDC2
label: UniProt:P06493 CDK1

PRKACB
label: UniProt:P22694 PRKACB

COT
label: ESTF
label: MAP3K8
label: UniProt:P41279 MAP3K8

TAK1 phosphorylates MKK6
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0004709
BFO_0000050: Interleukin-1 signaling
directly activates: BiochemicalReaction1075
directly activates: BiochemicalReaction6268
directly activates: Catalysis3211
directly activates: Catalysis399

p-RAF binds 14-3-3 beta/alpha
type: GO_0003674
BFO_0000050: RAF activation
directly activates: Transient dissociation of 14-3-3 upon Ras binding

Transient dissociation of 14-3-3 upon Ras binding
type: GO_0003674
BFO_0000050: RAF activation
directly activates: Stabilisation of RAS:RAF by 14-3-3

Stabilisation of RAS:RAF by 14-3-3
type: GO_0003674
BFO_0000050: RAF activation
directly activates: Stabilisation of RAF by further phosphorylation
directly activates: Catalysis447

Stabilisation of RAF by further phosphorylation
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0004713
BFO_0000050: RAF activation
directly activates: Activated RAF1 complex binds MEK

Phosphorylated human RAF1 binds to RAS:GTP complex
type: GO_0003674
BFO_0000050: RAF activation
directly activates: RAF1 phosphorylates MEK1
directly activates: RAF1 phosphorylates MEK2
directly activates: Catalysis448
directly activates: Catalysis449

Activated RAF1 complex binds MEK
type: GO_0003674
BFO_0000050: MEK activation
directly activates: RAF1 phosphorylates MEK1
directly activates: RAF1 phosphorylates MEK2
directly activates: Catalysis448
directly activates: Catalysis449

RAF1 phosphorylates MEK1
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0016301
BFO_0000050: RAF phosphorylates MEK
directly activates: MEK1 binds ERK-1

RAF1 phosphorylates MEK2
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0016301
BFO_0000050: RAF phosphorylates MEK
directly activates: MEK2 binds ERK-2

Caspase-1 precursor is cleaved releasing p10 and p20 subunits
type: GO_0003674
BFO_0000050: Interleukin-1 processing
directly activates: Formation of caspase-1 p10/p20 dimer

Formation of caspase-1 p10/p20 dimer
type: GO_0003674
BFO_0000050: Interleukin-1 processing
directly activates: Caspase-1 active tetramer formation

Caspase-1 active tetramer formation
type: GO_0003674
BFO_0000050: Interleukin-1 processing
directly activates: Interleukin-1 family precursors are cleaved by caspase-1
directly activates: Catalysis510
directly activates: Control105

Interleukin-1 family precursors are cleaved by caspase-1
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004197
BFO_0000050: Interleukin-1 processing
directly activates: Interleukin-1 family are secreted

Interleukin-1 family are secreted
type: GO_0003674
BFO_0000050: Interleukin-1 processing
directly activates: Interleukin-1 receptor type 1 binds Interleukin 1
directly activates: Interleukin-1 receptor type 2 binds Interleukin 1

Interleukin-1 receptor type 1 binds Interleukin 1
type: GO_0003674
BFO_0000050: Interleukin-1 signaling
directly activates: Interleukin-1 receptor type 1: Interleukin 1 binds Interleukin-1 receptor accessory protein, membrane associated isoform

Interleukin-1 receptor type 2 binds Interleukin 1
type: GO_0003674
BFO_0000050: Interleukin-1 signaling

IL1 receptor antagonist protein binds Interleukin 1 receptors
type: GO_0003674
BFO_0000050: Interleukin-1 signaling

Interleukin-1 receptor type 1: Interleukin 1 binds Interleukin-1 receptor accessory protein, membrane associated isoform
type: GO_0003674
BFO_0000050: Interleukin-1 signaling
directly activates: IL1R1:IL1:IL1RAP binds MYD88 homodimer

IL1R1:IL1:IL1RAP binds MYD88 homodimer
type: GO_0003674
BFO_0000050: Interleukin-1 signaling
directly activates: IL1R1:IL1:IL1RAP:MYD88 homodimer binds IRAK4

IL1R1:IL1:IL1RAP:MYD88 homodimer binds IRAK4
type: GO_0003674
BFO_0000050: Interleukin-1 signaling
directly activates: The Interleukin 1 receptor complex binds Tollip
directly activates: IRAK4 is activated by autophosphorylation

The Interleukin 1 receptor complex binds Tollip
type: GO_0003674
BFO_0000050: Interleukin-1 signaling

IRAK4 is activated by autophosphorylation
type: GO_0003674
BFO_0000050: Interleukin-1 signaling
directly activates: IRAK1 binds to MYD88 within the IL1R complex
directly activates: IRAK2 is phosphorylated downstream of IRAK4 following IL1 receptor activation

IRAK1 binds to MYD88 within the IL1R complex
type: GO_0003674
BFO_0000050: Interleukin-1 signaling
directly activates: IRAK4 phosphorylates IRAK1
directly activates: Catalysis511

IRAK4 phosphorylates IRAK1
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0004674
BFO_0000050: Interleukin-1 signaling
directly activates: IRAK4-activated IRAK1 autophosphorylates
directly activates: Catalysis512

IRAK4-activated IRAK1 autophosphorylates
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0004674
BFO_0000050: Interleukin-1 signaling
directly activates: Hyperphosphorylated IRAK1 associates with TRAF6

IRAK2 is phosphorylated downstream of IRAK4 following IL1 receptor activation
type: GO_0003674
BFO_0000050: Interleukin-1 signaling

Hyperphosphorylated IRAK1 associates with TRAF6
type: GO_0003674
BFO_0000050: Interleukin-1 signaling
directly activates: TRAF6 binding leads to IRAK1:TRAF6 release
directly activates: Control107

p62:MEKK3 binds to TRAF6
type: GO_0003674
BFO_0000050: Interleukin-1 signaling

TRAF6 binding leads to IRAK1:TRAF6 release
type: GO_0003674
BFO_0000050: Interleukin-1 signaling
directly activates: IRAK1 induces oligomerisation of TRAF6
directly activates: IRAK1 and 4 interact with Pellino1,2 and 3

IRAK1 induces oligomerisation of TRAF6
type: GO_0003674
BFO_0000050: Interleukin-1 signaling
directly activates: TRAF6 auto-ubiquitinates with Lys63-linked polyubiquitin chains
directly activates: Catalysis513

TRAF6 auto-ubiquitinates with Lys63-linked polyubiquitin chains
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004842
BFO_0000050: Interleukin-1 signaling
directly activates: Polyubiquitinated TRAF6 interacts with TAK1 complex

Polyubiquitinated TRAF6 interacts with TAK1 complex
type: GO_0003674
BFO_0000050: Interleukin-1 signaling
directly activates: TAK1 is activated within the TAK1 complex

TAK1 is activated within the TAK1 complex
type: GO_0003674
BFO_0000050: Interleukin-1 signaling
directly activates: TAK1 phosphorylates MKK6
directly activates: Activated TAK1 mediates phosphorylation of the IKK Complex
directly activates: Catalysis336
directly activates: Catalysis398

IRAK1 and 4 interact with Pellino1,2 and 3
type: GO_0003674
BFO_0000050: Interleukin-1 signaling
directly activates: IRAK1 and 4 can phosphorylate Pellino-1 and 2.
directly activates: Catalysis514

IRAK1 and 4 can phosphorylate Pellino-1 and 2.
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004674
BFO_0000050: Interleukin-1 signaling
directly activates: Pellino ubiquitinates IRAK1
directly activates: Catalysis515

Pellino ubiquitinates IRAK1
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004842
BFO_0000050: Interleukin-1 signaling
directly activates: NEMO binds polyubiquitinated IRAK1

NEMO binds polyubiquitinated IRAK1
type: GO_0003674
BFO_0000050: Interleukin-1 signaling

The IKKB complex phosphorylates NFkB p105
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0008384
BFO_0000050: Interleukin-1 signaling
directly activates: The SCF betaTrCP complex binds p-NFkB p105

The SCF betaTrCP complex binds p-NFkB p105
type: GO_0003674
BFO_0000050: Interleukin-1 signaling
directly activates: Beta-TrCP ubiquitinates then dissociates from p-NFKB p105
directly activates: Catalysis517

Beta-TrCP ubiquitinates then dissociates from p-NFKB p105
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004842
BFO_0000050: Interleukin-1 signaling

NFKB p105, TPL2 (COT) and ABIN2 form a stable complex
type: GO_0003674
BFO_0000050: Interleukin-1 signaling
directly activates: TPL2 phosphorylates MEK1, SEK1
directly activates: Catalysis518

TPL2 phosphorylates MEK1, SEK1
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: enabled by
  some values from: COT
type: Restriction
  on property: enabled by
  some values from: COT
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004709
BFO_0000050: Interleukin-1 signaling
directly activates: MEK1 binds ERK-1

IL2RB associates with JAK1
type: GO_0003674
BFO_0000050: Interleukin-2 signaling
directly activates: Interleukin-2 receptor alpha:IL2 binds Interleukin-2 receptor beta

IL2RG associates with JAK3
type: GO_0003674
BFO_0000050: Interleukin-2 signaling
BFO_0000050: Interleukin-7 signaling
directly activates: Interleukin-2: IL2 receptor alpha:beta binds IL2 receptor gamma subunit
directly activates: Interleukin-7:IL7RA:JAK1 binds Gc:JAK3

Interleukin-2 receptor alpha binds interleukin-2
type: GO_0003674
BFO_0000050: Interleukin-2 signaling
directly activates: Interleukin-2 receptor alpha:IL2 binds Interleukin-2 receptor beta

Interleukin-2 receptor alpha:IL2 binds Interleukin-2 receptor beta
type: GO_0003674
BFO_0000050: Interleukin-2 signaling
directly activates: Interleukin-2: IL2 receptor alpha:beta binds IL2 receptor gamma subunit

Interleukin-2: IL2 receptor alpha:beta binds IL2 receptor gamma subunit
type: GO_0003674
BFO_0000050: Interleukin-2 signaling
directly activates: Within the IL-2R complex JAK3 phosphorylates JAK1
directly activates: Catalysis519

Within the IL-2R complex JAK3 phosphorylates JAK1
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0004713
BFO_0000050: Interleukin-2 signaling
directly activates: JAK1 phosphorylates Y338, Y392 and Y510 of IL2RB
directly activates: Syk binds IL2RB
directly activates: Pyk2 associates with Jak3
directly activates: Catalysis520

JAK1 phosphorylates Y338, Y392 and Y510 of IL2RB
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0004713
BFO_0000050: Interleukin-2 signaling
directly activates: Phosphorylation of IL2RB Y338 enables SHC recruitment
directly activates: Phosphorylation of IL2RB Y338, Y392 or Y510 enables STAT recruitment

Phosphorylation of IL2RB Y338 enables SHC recruitment
type: GO_0003674
BFO_0000050: Interleukin-2 signaling
directly activates: SHC1 bound to IL2 receptor is phosphorylated
directly activates: Catalysis521

Phosphorylation of IL2RB Y338, Y392 or Y510 enables STAT recruitment
type: GO_0003674
BFO_0000050: Interleukin-2 signaling
directly activates: Recruited STAT5 is phosphorylated
directly activates: Catalysis523

SHC1 bound to IL2 receptor is phosphorylated
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004713
BFO_0000050: Interleukin-2 signaling
directly activates: Phosphorylated SHC1 recruits GRB2:GAB2
directly activates: Phosphorylated SHC recruits GRB2:SOS1

Phosphorylated SHC1 recruits GRB2:GAB2
type: GO_0003674
BFO_0000050: Interleukin receptor SHC signaling
directly activates: SHC1 mediates cytokine-induced phosphorylation of GAB2

SHC1 mediates cytokine-induced phosphorylation of GAB2
type: GO_0003674
BFO_0000050: Interleukin receptor SHC signaling
directly activates: Gab2 binds the p85 subunit of Class 1A PI3 kinases

Gab2 binds the p85 subunit of Class 1A PI3 kinases
type: GO_0003674
BFO_0000050: Interleukin receptor SHC signaling

Phosphorylated SHC recruits GRB2:SOS1
type: GO_0003674
BFO_0000050: Interleukin receptor SHC signaling
directly activates: SOS1 activates H-Ras
directly activates: BiochemicalReaction3817
directly activates: Catalysis1738
directly activates: Catalysis522

SOS1 activates H-Ras
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0005088
BFO_0000050: Interleukin receptor SHC signaling
directly activates: Transient dissociation of 14-3-3 upon Ras binding
directly activates: Phosphorylated human RAF1 binds to RAS:GTP complex

Phosphorylated SHC1 recruits SHIP
type: GO_0003674
BFO_0000050: Interleukin receptor SHC signaling
directly activates: The SHC1:SHIP1 complex is stabilized by GRB2

The SHC1:SHIP1 complex is stabilized by GRB2
type: GO_0003674
BFO_0000050: Interleukin receptor SHC signaling

Recruited STAT5 is phosphorylated
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0004713
BFO_0000050: Interleukin-2 signaling
directly activates: Phosphorylated STAT5 is released

Phosphorylated STAT5 is released
type: GO_0003674
BFO_0000050: Interleukin-2 signaling
directly activates: Phosphorylated STAT5 forms dimers

Phosphorylated STAT5 forms dimers
type: GO_0003674
BFO_0000050: Interleukin-2 signaling
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: STAT5 dimers translocate to the nucleus and bind to specific DNA sequences

STAT5 dimers translocate to the nucleus and bind to specific DNA sequences
type: GO_0003674
BFO_0000050: Interleukin-2 signaling
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling

Syk binds IL2RB
type: GO_0003674
BFO_0000050: Interleukin-2 signaling
directly activates: SYK is a substrate for JAK1
directly activates: Catalysis524

SYK is a substrate for JAK1
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0004713
BFO_0000050: Interleukin-2 signaling

Pyk2 associates with Jak3
type: GO_0003674
BFO_0000050: Interleukin-2 signaling
directly activates: Pyk2 is activated following IL2 stimulation

Pyk2 is activated following IL2 stimulation
type: GO_0003674
BFO_0000050: Interleukin-2 signaling

The common beta chain IL3RB binds JAK2
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: GM-CSF receptor alpha:GM-CSF binds Bc
directly activates: Interleukin-5:Interleukin-5 receptor alpha binds IL3RB:JAK2
directly activates: Interleukin-3 receptor alpha: Interleukin-3 binds IL3RB:JAK2

GM-CSF receptor alpha subunit binds GM-CSF
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: GM-CSF receptor alpha:GM-CSF binds Bc

GM-CSF receptor alpha:GM-CSF binds Bc
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: The receptor is activated

Interleukin-5 is a homodimer
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: Interleukin-5 receptor alpha subunit binds Interleukin-5

Interleukin-5 receptor alpha subunit binds Interleukin-5
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: Interleukin-5:Interleukin-5 receptor alpha binds IL3RB:JAK2

Interleukin-5:Interleukin-5 receptor alpha binds IL3RB:JAK2
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: The receptor is activated

Interleukin-3 receptor alpha subunit binds Interleukin-3
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: Interleukin-3 receptor alpha: Interleukin-3 binds IL3RB:JAK2

Interleukin-3 receptor alpha: Interleukin-3 binds IL3RB:JAK2
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: The receptor is activated

The receptor is activated
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: JAK2 is phosphorylated, activated
directly activates: Tyrosine kinases phosphorylate the receptor
directly activates: IL3RB is phosphorylated on Ser-585
directly activates: Catalysis525
directly activates: Catalysis527
directly activates: Catalysis531

JAK2 is phosphorylated, activated
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0004715
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: STAT5 is recruited by JAK2

STAT5 is recruited by JAK2
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: Activation of STAT5a/b by JAK2
directly activates: Catalysis526

Activation of STAT5a/b by JAK2
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0004713
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: p-STAT5 is released from the receptor complex

p-STAT5 is released from the receptor complex
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: Phosphorylated STAT5 forms dimers

Tyrosine kinases phosphorylate the receptor
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0004713
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: Recruitment of SHC1 is mediated by Y593 of the common beta chain
directly activates: SHP1 and SHP2 bind the common beta chain

Recruitment of SHC1 is mediated by Y593 of the common beta chain
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: SHC1 bound to the common beta chain becomes tyrosine phosphorylated
directly activates: Catalysis528

SHC1 bound to the common beta chain becomes tyrosine phosphorylated
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: Phosphorylated SHC1 recruits GRB2:GAB2
directly activates: Phosphorylated SHC recruits GRB2:SOS1

CBL, GRB2, FYN and PI3K p85 subunit are constitutively associated
type: GO_0003674
BFO_0000050: Regulation of signaling by CBL
directly activates: CBL is tyrosine phosphorylated
directly activates: Catalysis529

CBL is tyrosine phosphorylated
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004713
BFO_0000050: Regulation of signaling by CBL
directly activates: CBL ubiquitinates PI3K
directly activates: CBL binds CRK
directly activates: CBL binds B-cell linker protein
directly activates: CBL binds VAV

CBL ubiquitinates PI3K
type: GO_0003674
BFO_0000050: Regulation of signaling by CBL

CBL binds CRK
type: GO_0003674
BFO_0000050: Regulation of signaling by CBL
directly activates: CBL:CRKL binds RAPGEF1

CBL:CRKL binds RAPGEF1
type: GO_0003674
BFO_0000050: Regulation of signaling by CBL

CBL binds B-cell linker protein
type: GO_0003674
BFO_0000050: Regulation of signaling by CBL

CBL binds VAV
type: GO_0003674
BFO_0000050: Regulation of signaling by CBL

IL3 stimulation induces Vav binding to Tec kinase
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling

SHP1 and SHP2 bind the common beta chain
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: SHP1 and SHP2 dephosphorylate Y628 of IL3RB
directly activates: SHP2 can recruit GRB2
directly activates: Catalysis530

SHP1 and SHP2 dephosphorylate Y628 of IL3RB
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0004725
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling

SHP2 can recruit GRB2
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling

IL3RB is phosphorylated on Ser-585
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: enabled by
  some values from: PRKACB
type: Restriction
  on property: enabled by
  some values from: PRKACB
type: GO_0004691
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: p-S585-IL3RB binds 14-3-3 proteins

p-S585-IL3RB binds 14-3-3 proteins
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling
directly activates: 14-3-3 zeta binding allows recruitment of PI3K

14-3-3 zeta binding allows recruitment of PI3K
type: GO_0003674
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling

JAKs associate with IL6RB (gp130)
type: GO_0003674
BFO_0000050: Interleukin-6 signaling
directly activates: IL6:sIL6R binds to JAKs:IL6RB (gp130)
directly activates: IL6:IL6RA binds JAKs:IL6RB (gp130)
directly activates: Control109

Interleukin-6 binds to soluble IL-6 receptor
type: GO_0003674
BFO_0000050: Interleukin-6 signaling
directly activates: IL6:sIL6R binds sgp130
directly activates: IL6:sIL6R binds to JAKs:IL6RB (gp130)
directly activates: Control109

IL6:sIL6R binds sgp130
type: GO_0003674
BFO_0000050: Interleukin-6 signaling

Interleukin-6 binds to IL-6 receptor alpha subunit
type: GO_0003674
BFO_0000050: Interleukin-6 signaling
directly activates: IL6:IL6RA binds JAKs:IL6RB (gp130)

IL6:sIL6R binds to JAKs:IL6RB (gp130)
type: GO_0003674
BFO_0000050: Interleukin-6 signaling
directly activates: Assembly of a hexameric IL-6 receptor

IL6:IL6RA binds JAKs:IL6RB (gp130)
type: GO_0003674
BFO_0000050: Interleukin-6 signaling
directly activates: Assembly of a hexameric IL-6 receptor

Assembly of a hexameric IL-6 receptor
type: GO_0003674
BFO_0000050: Interleukin-6 signaling
directly activates: JAK activation

JAK activation
type: GO_0003674
BFO_0000050: Interleukin-6 signaling
directly activates: Phosphorylation of gp130

Phosphorylation of gp130
type: GO_0003674
BFO_0000050: Interleukin-6 signaling
directly activates: STATs bind gp130 phosphotyrosines
directly activates: SHP2 binds gp130 phosphotyrosine-759
directly activates: SOCS3 binds gp130

STATs bind gp130 phosphotyrosines
type: GO_0003674
BFO_0000050: Interleukin-6 signaling
directly activates: Tyrosine phosphorylation of STATs by IL6 receptor
directly activates: Catalysis532
directly activates: Control110

Tyrosine phosphorylation of STATs by IL6 receptor
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0004715
BFO_0000050: Interleukin-6 signaling
directly activates: Serine phosphorylation of STATs
directly activates: Phosphorylated STATs are released

Serine phosphorylation of STATs
type: GO_0003674
BFO_0000050: Interleukin-6 signaling
directly activates: Phosphorylated STATs are released

Phosphorylated STATs are released
type: GO_0003674
BFO_0000050: Interleukin-6 signaling
directly activates: Phosphorylated STAT1, STAT3 form dimers

Phosphorylated STAT1, STAT3 form dimers
type: GO_0003674
BFO_0000050: Interleukin-6 signaling
directly activates: STAT1/3 dimers translocate to the nucleus

STAT1/3 dimers translocate to the nucleus
type: GO_0003674
BFO_0000050: Interleukin-6 signaling

SHP2 binds gp130 phosphotyrosine-759
type: GO_0003674
BFO_0000050: Interleukin-6 signaling
directly activates: SHP2 is phosphorylated
directly activates: SHP2 binds c-Cbl upon IL-6 stimulation
directly activates: Catalysis533

SHP2 is phosphorylated
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0004715
BFO_0000050: Interleukin-6 signaling

SOCS3 binds gp130
type: GO_0003674
BFO_0000050: Interleukin-6 signaling

SHP2 binds c-Cbl upon IL-6 stimulation
type: GO_0003674
BFO_0000050: Interleukin-6 signaling

PPBSF is a complex of IL7 and HGFbeta
type: GO_0003674
BFO_0000050: Interleukin-7 signaling

IL7RA associates with JAK1
type: GO_0003674
BFO_0000050: Interleukin-7 signaling
directly activates: Interleukin-7 binds IL7RA:JAK1

Interleukin-7 binds IL7RA:JAK1
type: GO_0003674
BFO_0000050: Interleukin-7 signaling
directly activates: Interleukin-7:IL7RA:JAK1 binds Gc:JAK3

Interleukin-7:IL7RA:JAK1 binds Gc:JAK3
type: GO_0003674
BFO_0000050: Interleukin-7 signaling
directly activates: IL7RA is phosphorylated on Y449
directly activates: Catalysis534

IL7RA is phosphorylated on Y449
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005886
type: GO_0004715
BFO_0000050: Interleukin-7 signaling
directly activates: p(Y449)-IL7RA mediates STAT5 activation
directly activates: p85 binds p(Y449)-IL7RA

p(Y449)-IL7RA mediates STAT5 activation
type: GO_0003674
BFO_0000050: Interleukin-7 signaling

p85 binds p(Y449)-IL7RA
type: GO_0003674
BFO_0000050: Interleukin-7 signaling

Activated TAK1 mediates phosphorylation of the IKK Complex
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004674
BFO_0000050: Interleukin-1 signaling
directly activates: The IKKB complex phosphorylates NFkB p105
directly activates: BiochemicalReaction884
directly activates: Catalysis337
directly activates: Catalysis516

Inactivation of MEK1 by p34cdc2
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: enabled by
  some values from: CDC2
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004674
BFO_0000050: ERK1 activation

MEK1 binds ERK-1
type: GO_0003674
BFO_0000050: ERK1 activation
directly activates: MEK1 phosphorylates ERK-1
directly activates: Catalysis344
directly activates: Control57

MEK1 phosphorylates ERK-1
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004674
BFO_0000050: ERK1 activation
directly activates: Dissociation of phospho-ERK-1:MEK1

Dissociation of phospho-ERK-1:MEK1
type: GO_0003674
BFO_0000050: ERK1 activation
directly activates: Dimerisation of phospho-ERK-1

Dimerisation of phospho-ERK-1
type: GO_0003674
BFO_0000050: ERK1 activation
directly activates: Nuclear translocation of phospho-ERK-1 dimer

Nuclear translocation of phospho-ERK-1 dimer
type: GO_0000189
BFO_0000050: ERK1 activation
directly activates: BiochemicalReaction905
directly activates: BiochemicalReaction906
directly activates: BiochemicalReaction908
directly activates: Catalysis346
directly activates: Catalysis347
directly activates: Catalysis349

MEK2 binds ERK-2
type: GO_0003674
BFO_0000050: ERK2 activation
directly activates: MEK2 phosphorylates ERK-2
directly activates: Catalysis345

MEK2 phosphorylates ERK-2
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004674
BFO_0000050: ERK2 activation
directly activates: Dissociation of phospho-ERK-2:MEK2

Dissociation of phospho-ERK-2:MEK2
type: GO_0003674
BFO_0000050: ERK2 activation
directly activates: Dimerisation of phospho-ERK-2

Dimerisation of phospho-ERK-2
type: GO_0003674
BFO_0000050: ERK2 activation
directly activates: Nuclear translocation of phospho-ERK-2 dimer

Nuclear translocation of phospho-ERK-2 dimer
type: GO_0000189
BFO_0000050: ERK2 activation
directly activates: BiochemicalReaction905
directly activates: BiochemicalReaction906
directly activates: BiochemicalReaction908
directly activates: Catalysis346
directly activates: Catalysis347
directly activates: Catalysis349

ERK activation
type: GO_0008150
BFO_0000050: RAF/MAP kinase cascade

ERK1 activation
type: GO_0008150
BFO_0000050: ERK activation

ERK2 activation
type: GO_0008150
BFO_0000050: ERK activation

RAF/MAP kinase cascade
type: GO_0008150
BFO_0000050: Interleukin-2 signaling

RAF activation
type: GO_0008150
BFO_0000050: RAF/MAP kinase cascade

MEK activation
type: GO_0008150
BFO_0000050: RAF/MAP kinase cascade

RAF phosphorylates MEK
type: GO_0008150
BFO_0000050: MEK activation

Signaling by Interleukins
type: GO_0008150

Interleukin-1 processing
type: GO_0008150
BFO_0000050: Signaling by Interleukins

Interleukin-1 signaling
type: GO_0008150
BFO_0000050: Signaling by Interleukins

Interleukin-2 signaling
type: GO_0008150
BFO_0000050: Signaling by Interleukins

Interleukin receptor SHC signaling
type: GO_0008150
BFO_0000050: Interleukin-2 signaling
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling

Interleukin-3, 5 and GM-CSF signaling
type: GO_0008150
BFO_0000050: Signaling by Interleukins

Regulation of signaling by CBL
type: GO_0008150
BFO_0000050: Interleukin-3, 5 and GM-CSF signaling

Interleukin-6 signaling
type: GO_0008150
BFO_0000050: Signaling by Interleukins

Interleukin-7 signaling
type: GO_0008150
BFO_0000050: Signaling by Interleukins