Pathological roles of MAPK signaling pathways in human diseases

Abstract

The mammalian family of mitogen-activated protein kinases (MAPKs) includes extracellular signal-regulated kinase (ERK), p38, and c-Jun NH(2)-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.

Abnormal Activity of the MAPK- and cAMP-Associated Signaling Pathways in Frontal Cortical Areas in Postmortem Brain in Schizophrenia

“…In fact, relatively small changes are perhaps not unexpected, as more substantial changes in expression of these proteins are associated with oncogenic, apoptotic, and excitotoxic events (Huang et al, 2009;Kim and Choi, 2010;Soriano et al, 2008;von Engelhardt et al, 2007;Wagner and Nebreda, 2009). …”

Exploring the phosphoproteome profiles duringXenopusegg activation by calcium stimulation using a fully automated phosphopeptide purification system

“…So, it was suggested that suppression of ionization of multiply phosphorylated peptides by mono-phosphorylated peptides on MS was reduced in the samples prepared by the 4-step elution method. In addition to the enhanced resolution of mono-phosphorylated peptides, the stepwise elution method was especially useful for identification of multiply phosphorylated sites that may be linked to the receptor signalling process because kinases involved in the process often require multi-site Xenopus egg phosphoproteome phosphorylation for their activation (18,19). A fully automated phosphopeptide purification system involving optimized 4-step elution from a titania column is more useful than the original 1-step method for lessbiased phosphoproteome analysis.…”

Untitled

“…Blocking ERK1/2 activation reduces mechanical and/ or thermal hypersensitivity following tissue injury/inflammation [8,10,11]. Phosphorylated ERK1/2 have a series of downstream targets including the mitogen-and stress-activated kinases 1 and 2 (MKS1/2) [12]. However, the ERK1/2 activation-induced transcriptional changes appear to be mediated predominantly by MSK1/2 [13,14].…”