Pathway Report

Basic Information

Name	mapkkk cascade
GO Link	ID: GO:0000165 Name: MAPK cascade Type: biological process
Description	Genes annotated by the GO term GO:0000165. Cascade of at least three protein kinase activities culminating in the phosphorylation and activation of a MAP kinase. MAPKKK cascades lie downstream of numerous signaling pathways.
No. of Studies (Positive/Negative)	4 (4/0)

Positive relationship between mapkkk cascade and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
extracellular-regulated protein kinase (ERK) pathway	Yuan, 2010	patients and normal controls		Levels of most studied protein members of the ERK cascade we...... Levels of most studied protein members of the ERK cascade were lower in individuals with psychiatric disorders than controls More...

Positive relationships between mapkkk cascade and other components at different levels (count: 8)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name(Name in Literature)	Type	Reference	Research Type	Relation Description
Name in Literature	Related Components
signal-regulated kinase (ERK)		BDNF(BDNF)	gene	Schmidt HD, 2010	animal model	BDNF levels as well as expression of pCREB and pERK were ele...... BDNF levels as well as expression of pCREB and pERK were elevated in the hippocampus of adult mice receiving peripheral BDNF More...
ERK		Disrupted in schizophrenia 1 protein(DISC1)	protein	Hashimoto, 2006	patients and normal controls; cell model	In primary neuronal culture, knockdown of endogenous DISC1 p...... In primary neuronal culture, knockdown of endogenous DISC1 protein by small interfering RNA resulted in the suppression of phosphorylation of ERK and Akt, whose signaling pathways are implicated in MDD. When effects of sDISC1 (Ser704) and cDISC1 (Cys704) proteins were examined separately, phosphorylation of ERK was greater in sDISC1 compared with cDISC1. More...
ERK pathway		Cyclic AMP-responsive element-binding protein 1(cAMP response element-binding protein (CREB))	protein	Qi X, 2009	animal model	The phosphorylation of the cyclic AMP-responsive-element-bin...... The phosphorylation of the cyclic AMP-responsive-element-binding protein (CREB) was decreased following the ERK pathway inhibition More...
ERK		Brain-derived neurotrophic factor(BDNF)	protein	Schmidt HD, 2010	animal model	Expression of pCREB and pERK were elevated in the hippocampu...... Expression of pCREB and pERK were elevated in the hippocampus of adult mice receiving peripheral BDNF More...
ERK pathway		U0126(U0126)	molecule	Qi X, 2009	animal model	U0126, a specific inhibitor of ERK upstream activator U0126, a specific inhibitor of ERK upstream activator
ERK pathway		anhedonic-like behavior from animal model(anhedonic-like behavior)	cognition and behavior	Qi X, 2009	animal model	The inhibition of the ERK pathway in dHP resulted in anhedon...... The inhibition of the ERK pathway in dHP resulted in anhedonia and anxiety-like behavior, and the ERK pathway inhibition in the mPFC induced anhedonia and locomotor impairment in rats More...
ERK pathway		Anxiety-like behaviors from animal model(anxiety-like behavior)	cognition and behavior	Qi X, 2009	animal model	The inhibition of the ERK pathway in dHP resulted in anhedon...... The inhibition of the ERK pathway in dHP resulted in anhedonia and anxiety-like behavior, and the ERK pathway inhibition in the mPFC induced anhedonia and locomotor impairment in rats More...
ERK pathway		Irritability(increased irritability)	symptoms	Qi X, 2009	animal model	The inhibition of the ERK pathway in dHP resulted in anhedon...... The inhibition of the ERK pathway in dHP resulted in anhedonia and anxiety-like behavior, and the ERK pathway inhibition in the mPFC induced anhedonia and locomotor impairment in rats More...

Positive relationship network of mapkkk cascade in MK4MDD

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between mapkkk cascade and MDD (count: 0)

Negative relationships between mapkkk cascade and other components at different levels (count: 0)

Pathway mapkkk cascade related genes in MK4MDD (count: 11)

Approved Symbol	Approved Name	Type	No. of Studies (Positive/Negative)
IL1B	interleukin 1, beta	Literature-origin; SNP mapped; Protein mapped	3(2/1)
INS	insulin	Literature-origin; Protein mapped	1(1/0)
MAPK1	mitogen-activated protein kinase 1	Literature-origin	2(2/0)
IL18	interleukin 18 (interferon-gamma-inducing factor)	Literature-origin; Protein mapped	1(1/0)
FGFR3	fibroblast growth factor receptor 3	Literature-origin	2(2/0)
TNF	tumor necrosis factor	Literature-origin; SNP mapped; Protein mapped	5(5/0)
NRG1	neuregulin 1	Literature-origin; Protein mapped	2(1/1)
CCL2	chemokine (C-C motif) ligand 2	Literature-origin; SNP mapped; Protein mapped	2(1/1)
PTK2B	protein tyrosine kinase 2 beta	Literature-origin	2(2/0)
FGFR1	fibroblast growth factor receptor 1	Literature-origin	3(3/0)
DUSP4	dual specificity phosphatase 4	Literature-origin	1(1/0)