Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases
Tóm tắt
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.
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Buxade, M., J. L. Parra-Palau, and C. G. Proud. 2008. The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating kinases). Front. Biosci. 13:5359-5373.
Carriere, A., H. Ray, J. Blenis, and P. P. Roux. 2008. The RSK factors of activating the Ras/MAPK signaling cascade. Front. Biosci. 13:4258-4275.
Chen, R. H., P. C. Juo, T. Curran, and J. Blenis. 1996. Phosphorylation of c-Fos at the C-terminus enhances its transforming activity. Oncogene 12:1493-1502.
Phosphorylation of Cdc25C by pp90Rsk contributes to a G(2) cell cycle arrest in Xenopus cycling egg extracts. 2005
Crowe, D. L. 2004. Induction of p97MAPK expression regulates collagen mediated inhibition of proliferation and migration in human squamous cell carcinoma lines. Int. J. Oncol. 24:1159-1163.
Davie, J. R. 2003. MSK1 and MSK2 mediate mitogen- and stress-induced phosphorylation of histone H3: a controversy resolved. Sci. STKE 2003:PE33.
Davis, I. J., T. G. Hazel, R. H. Chen, J. Blenis, and L. F. Lau. 1993. Functional domains and phosphorylation of the orphan receptor Nur77. Mol. Endocrinol. 7:953-964.
Dreiza, C. M., et al. 2005. Transducible heat shock protein 20 (HSP20) phosphopeptide alters cytoskeletal dynamics. FASEB J. 19:261-263.
Gaestel, M. 2008. Specificity of signaling from MAPKs to MAPKAPKs: kinases' tango nuevo. Front. Biosci. 13:6050-6059. doi:http://dx.doi.org/10.2741/3136.
Gerits, N., et al. 2009. The transcriptional regulation and cell-specific expression of the MAPK-activated protein kinase MK5. Cell Mol. Biol. Lett. 14:548-574.
Llanos, S., A. Cuadrado, and M. Serrano. 2009. MSK2 inhibits p53 activity in the absence of stress. Sci. Signal 2:ra57.
Meloche, S., B. G. Beatty, and J. Pellerin. 1996. Primary structure, expression and chromosomal locus of a human homolog of rat ERK3. Oncogene 13:1575-1579.
Pearson, G., et al. 2001. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocrinol. Rev. 22:153-183.
Perander, M., S. M. Keyse, and O. M. Seternes. 2008. Does MK5 reconcile classical and atypical MAP kinases? Front. Biosci. 13:4617-4624.
Ronkina, N., A. Kotlyarov, and M. Gaestel. 2008. MK2 and MK3—a pair of isoenzymes? Front. Biosci. 13:5511-5521.
Smith, J. A., et al. 2005. Identification of the first specific inhibitor of p90 ribosomal S6 kinase (RSK) reveals an unexpected role for RSK in cancer cell proliferation. Cancer Res. 65:1027-1034.
Thornton, T. M., and M. Rincon. 2009. Non-classical p38 map kinase functions: cell cycle checkpoints and survival. Int. J. Biol. Sci. 5:44-51.
Wendel, H. G., et al. 2007. Dissecting eIF4E action in tumorigenesis. Genes Dev. 21:3232-3237.