4ic7
Crystal structure of the ERK5 kinase domain in complex with an MKK5 binding fragmentCrystal structure of the ERK5 kinase domain in complex with an MKK5 binding fragment
Template:ABSTRACT PUBMED 23382384
FunctionFunction
[MK07_HUMAN] Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction.[1] [2] [3] [4] [5] [MP2K5_HUMAN] Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis.[6] [7]
About this StructureAbout this Structure
4ic7 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
- ↑ Glatz G, Gogl G, Alexa A, Remenyi A. Structural mechanism for the specific assembly and activation of the extracellular signal regulated kinase 5 (ERK5) module. J Biol Chem. 2013 Mar 22;288(12):8596-609. doi: 10.1074/jbc.M113.452235. Epub, 2013 Feb 4. PMID:23382384 doi:10.1074/jbc.M113.452235
- ↑ Kato Y, Kravchenko VV, Tapping RI, Han J, Ulevitch RJ, Lee JD. BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C. EMBO J. 1997 Dec 1;16(23):7054-66. PMID:9384584 doi:10.1093/emboj/16.23.7054
- ↑ Kato Y, Tapping RI, Huang S, Watson MH, Ulevitch RJ, Lee JD. Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor. Nature. 1998 Oct 15;395(6703):713-6. PMID:9790194 doi:10.1038/27234
- ↑ Hayashi M, Tapping RI, Chao TH, Lo JF, King CC, Yang Y, Lee JD. BMK1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinase. J Biol Chem. 2001 Mar 23;276(12):8631-4. Epub 2001 Jan 31. PMID:11254654 doi:10.1074/jbc.C000838200
- ↑ Dong F, Gutkind JS, Larner AC. Granulocyte colony-stimulating factor induces ERK5 activation, which is differentially regulated by protein-tyrosine kinases and protein kinase C. Regulation of cell proliferation and survival. J Biol Chem. 2001 Apr 6;276(14):10811-6. Epub 2001 Jan 17. PMID:11278431 doi:10.1074/jbc.M008748200
- ↑ Yang Q, Liao L, Deng X, Chen R, Gray NS, Yates JR 3rd, Lee JD. BMK1 is involved in the regulation of p53 through disrupting the PML-MDM2 interaction. Oncogene. 2012 Aug 6. doi: 10.1038/onc.2012.332. PMID:22869143 doi:10.1038/onc.2012.332
- ↑ Zhou G, Bao ZQ, Dixon JE. Components of a new human protein kinase signal transduction pathway. J Biol Chem. 1995 May 26;270(21):12665-9. PMID:7759517
- ↑ Kato Y, Kravchenko VV, Tapping RI, Han J, Ulevitch RJ, Lee JD. BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C. EMBO J. 1997 Dec 1;16(23):7054-66. PMID:9384584 doi:10.1093/emboj/16.23.7054