2011/03/01 by Marie Cargnello, Philippe P. Roux · 3,286 citations
Biochemistry, Genetics and Molecular Biology · #ASK1 #Biology #Cell biology #Cellular Mechanics and Interactions #Cyclin-dependent kinase 2 #Kinase #MAP kinase kinase kinase #MAP2K7 #MAPK/ERK pathway #Melanoma and MAPK Pathways #Mitogen-activated protein kinase #Mitogen-activated protein kinase kinase #P70-S6 Kinase 1 #Protein Kinase Regulation and GTPase Signaling #Protein kinase A #Protein kinase B #Ribosomal s6 kinase #Signal transduction #p38 mitogen-activated protein kinases
paper · doi:10.1128/mmbr.00031-10
published in Microbiology and Molecular Biology Reviews 75(1), 50-83 (American Society for Microbiology)
openalex publication_date 2011/03/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06
The mitogen-activated protein kinases (MAPKs) regulate diverse cellular programs by relaying extracellular signals to intracellular responses. In mammals, there are more than a dozen MAPK enzymes that coordinately regulate cell proliferation, differentiation, motility, and survival. The best known are the conventional MAPKs, which include the extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun amino-terminal kinases 1 to 3 (JNK1 to -3), p38 (α, β, γ, and δ), and ERK5 families. There are additional, atypical MAPK enzymes, including ERK3/4, ERK7/8, and Nemo-like kinase (NLK), which have distinct regulation and functions. Together, the MAPKs regulate a large number of substrates, including members of a family of protein Ser/Thr kinases termed MAPK-activated protein kinases (MAPKAPKs). The MAPKAPKs are related enzymes that respond to extracellular stimulation through direct MAPK-dependent activation loop phosphorylation and kinase activation. There are five MAPKAPK subfamilies: the p90 ribosomal S6 kinase (RSK), the mitogen- and stress-activated kinase (MSK), the MAPK-interacting kinase (MNK), the MAPK-activated protein kinase 2/3 (MK2/3), and MK5 (also known as p38-regulated/activated protein kinase [PRAK]). These enzymes have diverse biological functions, including regulation of nucleosome and gene expression, mRNA stability and translation, and cell proliferation and survival. Here we review the mechanisms of MAPKAPK activation by the different MAPKs and discuss their physiological roles based on established substrates and recent discoveries.