Eun Kyung Kim, Eui-Ju Choi

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea

Received 10 September 2009; revised 26 November 2009; Accepted 1 December 2009. Available online 14 January 2010.

Corresponding author : Eui-Ju Choi, Tel.: + 82 2 3290 3446.

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; Aβ, 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