ERK and p38 MAPK-Activated Protein Kinases: a Family of Protein Kinases with Diverse Biological Functions
Tóm tắt
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.
Từ khóa
Tài liệu tham khảo
Ballif, B. A., and J. Blenis. 2001. Molecular mechanisms mediating mammalian mitogen-activated protein kinase (MAPK) kinase (MEK)-MAPK cell survival signals.Cell Growth Differ.12:397-408.
Chen, R. H., P. C. Juo, T. Curran, and J. Blenis. 1996 . Phosphorylation of c-Fos at the C-terminus enhances its transforming activity. Oncogene12:1493-1502.
Davie J. R. 2003. MSK1 and MSK2 mediate mitogen- and stress-induced phosphorylation of histone H3: a controversy resolved. Science STKE 2003: PE33.
Flynn A. R. G. Vries and C. G. Proud. 1997 . Signalling pathways which regulate eIF4E. Biochem. Soc. Trans. 25 : 192S.
Kohno, M., and J. Pouyssegur. 2003. Pharmacological inhibitors of the ERK signaling pathway: application as anticancer drugs. Prog. Cell Cycle Res.5:219-224.
Mercer, K. E., and C. A. Pritchard. 2003. Raf proteins and cancer: B-Raf is identified as a mutational target.Biochim. Biophys. Acta1653:25-40.
Parra-Palau J. L. G. C. Scheper M. L. Wilson and C. G. Proud. 2003. Features in the N- and C-termini of the MAP kinase-interacting kinase Mnk1 mediate its nucleocytoplasmic shuttling. J. Biol. Chem. 278: 44197-44204.
Pearson, G., F. Robinson, T. Beers Gibson, B. E. Xu, M. Karandikar, K. Berman, and M. H. Cobb. 2001. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocrinol. Rev.22:153-183.
Quan, L. T., A. Caputo, R. C. Bleackley, D. J. Pickup, and G. S. Salvesen. 1995.Granzyme B is inhibited by the cowpox virus serpin cytokine response modifier A. J. Biol. Chem.270:10377-10379.
Schuck S. A. Soloaga G. Schratt J. S. Arthur and A. Nordheim. 2003. The kinase MSK1 is required for induction of c-fos by lysophosphatidic acid in mouse embryonic stem cells. BMC Mol. Biol. 4 : 6.
Tran, H., F. Maurer, and Y. Nagamine. 2003.Stabilization of urokinase and urokinase receptor mRNAs by HuR is linked to its cytoplasmic accumulation induced by activated mitogen-activated protein kinase-activated protein kinase 2. Mol. Cell. Biol.23:7177-7188.