Review
Pathological roles of MAPK signaling pathways in human diseases

https://doi.org/10.1016/j.bbadis.2009.12.009Get rights and content
Under an Elsevier user license
open archive

Abstract

The mammalian family of mitogen-activated protein kinases (MAPKs) includes extracellular signal-regulated kinase (ERK), p38, and c-Jun NH2-terminal kinase (JNK), with each MAPK signaling pathway consisting of at least three components, a MAPK kinase kinase (MAP3K), a MAPK kinase (MAP2K), and a MAPK. The MAPK pathways are activated by diverse extracellular and intracellular stimuli including peptide growth factors, cytokines, hormones, and various cellular stressors such as oxidative stress and endoplasmic reticulum stress. These signaling pathways regulate a variety of cellular activities including proliferation, differentiation, survival, and death. Deviation from the strict control of MAPK signaling pathways has been implicated in the development of many human diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and various types of cancers. Persistent activation of the JNK or p38 signaling pathways has been suggested to mediate neuronal apoptosis in AD, PD, and ALS, whereas the ERK signaling pathway plays a key role in several steps of tumorigenesis including cancer cell proliferation, migration, and invasion. In this review, we summarize recent findings on the roles of MAPK signaling pathways in human disorders, focusing on cancer and neurodegenerative diseases including AD, PD, and ALS.

Abbreviations

MAPK
mitogen-activated protein kinase
ERK
extracellular signal-regulated kinase
JNK
c-Jun NH2-terminal kinase
MAP3K
MAPK kinase kinase
MAP2K
MAPK kinase
KSR
kinase suppressor of Ras-1
MP1
MEK partner 1
JIP
JNK-interacting protein
TNF
tumor necrosis factor
IL
interleukin
MLK
mixed-lineage kinase
RTK
receptor tyrosine kinase
ASK1
apoptosis signal-regulating kinase 1
ROS
reactive oxygen species
LPS
lipopolysaccharide
ER
endoplasmic reticulum
AD
Alzheimer's disease
amyloid-β
APP
amyloid precursor protein
PD
Parkinson's disease
LB
Lewy body
LRRK2
leucine-rich repeat kinase 2
PINK1
PTEN-induced kinase 1
MPTP
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
iNOS
inducible NO synthase
TTRAP
TRAF- and TNF receptor-associated protein
ALS
amyotrophic lateral sclerosis
SOD1
superoxide dismutase 1
TDP-43
TAR DNA-binding protein-43
FUS
fused in sarcoma
TLS
translated in liposarcoma
FasL
Fas ligand
EGFR
epidermal growth factor receptor

Keywords

MAPK
JNK
p38
Neurodegenerative disease
Cancer

Cited by (0)