Article

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

ABSTRACT

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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    • "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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