ERK and p38 MAPK-Activated Protein Kinases: a Family of Protein Kinases with Diverse Biological Functions

Department of Molecular and Cell Biology, Harvard University, Cambridge, Massachusetts, United States
Microbiology and Molecular Biology Reviews (Impact Factor: 14.61). 07/2004; 68(2):320-44. DOI: 10.1128/MMBR.68.2.320-344.2004
Source: PubMed


Conserved signaling pathways that activate the mitogen-activated protein kinases (MAPKs) are involved in relaying extracellular stimulations to intracellular responses. The MAPKs coordinately regulate cell proliferation, differentiation, motility, and survival, which are functions also known to be mediated by members of a growing family of MAPK-activated protein kinases (MKs; formerly known as MAPKAP kinases). The MKs are related serine/threonine kinases that respond to mitogenic and stress stimuli through proline-directed phosphorylation and activation of the kinase domain by extracellular signal-regulated kinases 1 and 2 and p38 MAPKs. There are currently 11 vertebrate MKs in five subfamilies based on primary sequence homology: the ribosomal S6 kinases, the mitogen- and stress-activated kinases, the MAPK-interacting kinases, MAPK-activated protein kinases 2 and 3, and MK5. In the last 5 years, several MK substrates have been identified, which has helped tremendously to identify the biological role of the members of this family. Together with data from the study of MK-knockout mice, the identities of the MK substrates indicate that they play important roles in diverse biological processes, including mRNA translation, cell proliferation and survival, and the nuclear genomic response to mitogens and cellular stresses. In this article, we review the existing data on the MKs and discuss their physiological functions based on recent discoveries.

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    • "protein kinase (ERK), c-JUN N-terminal kinase/stressactivated protein kinases (JNK/SAP) and p38MAPK [4]. The MAPK signaling pathway is involved in various kinds of cellular processes including differentiation, development, proliferation, and survival, as well as cell death, depending on cell type and stimulus [5] [6]. Pulpal p38MAPK signaling is activated by LPS stimulation during the induction of local proinflammatory response [7] [8] [9]. "
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    ABSTRACT: Porphyromonas gingivalis is considered with inducing pulpal inflammation and has lipopolysaccharide (LPS) as an inflammatory stimulator. GV1001 peptide has anticancer and anti-inflammation activity due to inhibiting activation of signaling molecules after penetration into the various types of cells. Therefore, this study examined inhibitory effect of GV1001 on dental pulp cells (hDPCs) stimulated by P. gingivalis LPS. The intracellular distribution of GV1001 was analyzed by confocal microscopy. Real-time RT-PCR was performed to determine the expression levels of TNF- α and IL-6 cytokines. The role of signaling by MAP kinases (ERK and p38) was explored using Western blot analysis. The effect of GV1001 peptide on hDPCs viability was measured by MTT assay. GV1001 was predominantly located in hDPC cytoplasm. The peptide inhibited P. gingivalis LPS-induced TNF- α and IL-6 production in hDPCs without significant cytotoxicity. Furthermore, GV1001 treatment markedly inhibited the phosphorylation of MAP kinases (ERK and p38) in LPS-stimulated hDPCs. GV1001 may prevent P. gingivalis LPS-induced inflammation of apical tissue. Also, these findings provide mechanistic insight into how GV1001 peptide causes anti-inflammatory actions in LPS-stimulated pulpitis without significantly affecting cell viability.
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    • "ERK is a member of the mitogen-activated protein kinase (MAPK) family that regulates critical phases of cell growth, including proliferation, differentiation, transcription regulation, and development141516. It is well known that MAPKs play pivotal roles in carcinogenesis[17]and that the MAPK pathway is a key downstream signaling pathway regulated by epidermal growth factor receptor (EGFR) signaling in a number of cancers[14,15]. Up to 90% of head and neck squamous cell carcinomas (HNSCC), including OSCC, are known to overexpress EGFR and this leads to excessive activation of the EGFR signaling pathway[18,19]. Activation of EGFR-Raf-MAPK/ERK kinase-ERK signaling has been reported in several cancers, including HNSCC, and has led to the discovery of novel anticancer drugs. "
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    ABSTRACT: Molecularly targeted drugs are used in the treatment of a variety of malignant tumors, but this approach to developing novel therapies for oral squamous cell carcinoma (OSCC) has lagged behind the progress seen for other cancers. We have attempted to find appropriate molecular targets for OSCC and identified cell division cycle associated 5 (CDCA5) as a cancer-related gene which was overexpressed in all the human OSCC cells tested by microarray analysis. In this study, we investigated the expression and function of CDCA5 in OSCC. First, we confirmed that CDCA5 was overexpressed in 4 human OSCC cell lines by quantitative RT-PCR and Western blotting. We then tested the effect of synthetic small interfering RNAs specific for CDCA5 on the growth and invasion of human OSCC cells. Knockdown of CDCA5 markedly inhibited the growth of OSCC cells in vitro and in vivo. We also examined the expression of CDCA5 protein in 80 cases of OSCC immunohistochemically and found a significant association between CDCA5 expression levels and overall survival. These results suggest that CDCA5 functions as a critical gene supporting OSCC progression and that targeting CDCA5 may be a useful therapeutic strategy for OSCC.
    Preview · Article · Oct 2015 · Oncotarget
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    • "Many different stimuli, including growth factors, cytokines and viral infection activate the ERK pathway. P38 mitogenactivated protein kinases are responsive as same as JNK, and involved in cell differentiation, apoptosis and autophagy (Johnson and Lapadat, 2002; Roux and Blenis, 2004; Xia et al., 1995). The phosphorylation levels of p38, ERK and JNK after bacterial stimulation were each highly elevated by 30 min, which indicates that cell signaling was activated in the E. sinensis hemocyte culture system described here. "
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