Table 1

Interdependency of distinct signaling pathways

ProteinSubstrateAction
JAK2 STATs Signaling initiation 
 MAPK Signaling initiation 
 PI3K Signaling initiation 
 IκB Degradation (phosphorylation) 
PDK1 PKB Activation (phosphorylation) 
 IKKβ Activation (phosphorylation) 
RAS RAF Activation (phosphorylation) 
 PI3K Activation 
PP2A IKK Inhibition (negative feedback) 
 PKB Inhibition (negative feedback) 
SOCS1 STAT5 Inhibition (negative feedback) 
 NF-κB Inhibition (negative feedback) 
PIAS1 JAK2 Inhibition (negative feedback) 
 RelA Inhibition DNA binding 
PI3K PKB Activation (indirect) 
 NF-κB Activation (phosphorylation) 
PKB mTORC1 Activation (phosphorylation and indirect) 
 TSC2 Inhibition (phosphorylation) 
 RelA Enhanced activity (phosphorylation) 
 IKKβ Activation (indirect) 
p38 MAPK NF-κB Regulation DNA binding 
ERK TSC2 Inhibition (phosphorylation) 
NF-κB SOCS1 Increased production 
STAT5 NF-κB Activation (phosphorylation) 
IKKβ IκBα Degradation (phosphorylation) 
 TSC1 Inhibition (phosphorylation) 
ProteinSubstrateAction
JAK2 STATs Signaling initiation 
 MAPK Signaling initiation 
 PI3K Signaling initiation 
 IκB Degradation (phosphorylation) 
PDK1 PKB Activation (phosphorylation) 
 IKKβ Activation (phosphorylation) 
RAS RAF Activation (phosphorylation) 
 PI3K Activation 
PP2A IKK Inhibition (negative feedback) 
 PKB Inhibition (negative feedback) 
SOCS1 STAT5 Inhibition (negative feedback) 
 NF-κB Inhibition (negative feedback) 
PIAS1 JAK2 Inhibition (negative feedback) 
 RelA Inhibition DNA binding 
PI3K PKB Activation (indirect) 
 NF-κB Activation (phosphorylation) 
PKB mTORC1 Activation (phosphorylation and indirect) 
 TSC2 Inhibition (phosphorylation) 
 RelA Enhanced activity (phosphorylation) 
 IKKβ Activation (indirect) 
p38 MAPK NF-κB Regulation DNA binding 
ERK TSC2 Inhibition (phosphorylation) 
NF-κB SOCS1 Increased production 
STAT5 NF-κB Activation (phosphorylation) 
IKKβ IκBα Degradation (phosphorylation) 
 TSC1 Inhibition (phosphorylation) 

Although the various signaling cascades regulated by the GM-CSF receptor are often regarded as separate entities, they are actually interrelated, sharing proteins regulating their activation or inhibition, or even directly influencing each other. Proteins involved in more than 1 signaling cascade are listed, together with the proteins they regulate and the actions they express toward them. If 1 of the regulated proteins is regarded as a principle target, this protein is underlined.

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