MAPK4 explained

Mitogen-activated protein kinase 4 is an enzyme that in humans is encoded by the MAPK4 gene.^{[1] [2]}

Mitogen-activated protein kinase 4 is a member of the mitogen-activated protein kinase family. Tyrosine kinase growth factor receptors activate mitogen-activated protein kinases which then translocate into the nucleus where it phosphorylates nuclear targets.^[2]

The Arabidopsis MAPK4 is important in signalling ^[3]

Mechanistically, MAPK4 directly bound and activated AKT by phosphorylation of the activation loop at threonine 308. It also activated mTORC2 to phosphorylate AKT at serine 473 for full activation. MAPK4 overexpression induced oncogenic outcomes, including transforming prostate epithelial cells into anchorage-independent growth, and MAPK4 knockdown inhibited cancer cell proliferation, anchorage-independent growth, and xenograft growth.^[4]

Further reading

• Seger R, Krebs EG . The MAPK signaling cascade . FASEB Journal . 9 . 9 . 726–35 . June 1995 . 7601337 . 10.1096/fasebj.9.9.7601337. free . 23298305 .
• Davis RJ . Transcriptional regulation by MAP kinases . Molecular Reproduction and Development . 42 . 4 . 459–67 . December 1995 . 8607977 . 10.1002/mrd.1080420414 . 12842112 .
• Robinson MJ, Cobb MH . Mitogen-activated protein kinase pathways . Current Opinion in Cell Biology . 9 . 2 . 180–6 . April 1997 . 9069255 . 10.1016/S0955-0674(97)80061-0 .
• Gonzalez FA, Raden DL, Rigby MR, Davis RJ . Heterogeneous expression of four MAP kinase isoforms in human tissues . FEBS Letters . 304 . 2–3 . 170–8 . June 1992 . 1319925 . 10.1016/0014-5793(92)80612-K . 42548392 .
• Zhu AX, Zhao Y, Moller DE, Flier JS . Cloning and characterization of p97MAPK, a novel human homolog of rat ERK-3 . Molecular and Cellular Biology . 14 . 12 . 8202–11 . December 1994 . 7969157 . 359359 . 10.1128/mcb.14.12.8202 .
• Kinet S, Bernard F, Mongellaz C, Perreau M, Goldman FD, Taylor N . gp120-mediated induction of the MAPK cascade is dependent on the activation state of CD4(+) lymphocytes . Blood . 100 . 7 . 2546–53 . October 2002 . 12239168 . 10.1182/blood-2002-03-0819 . free .
• Sun M, Wei Y, Yao L, Xie J, Chen X, Wang H, Jiang J, Gu J . 6 . Identification of extracellular signal-regulated kinase 3 as a new interaction partner of cyclin D3 . Biochemical and Biophysical Research Communications . 340 . 1 . 209–14 . February 2006 . 16360641 . 10.1016/j.bbrc.2005.12.003 .
• Kant S, Schumacher S, Singh MK, Kispert A, Kotlyarov A, Gaestel M . Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5 . The Journal of Biological Chemistry . 281 . 46 . 35511–9 . November 2006 . 16973613 . 10.1074/jbc.M606693200 . free .

External links

• MAP Kinase Resource

Notes and References

1. Li L, Wysk M, Gonzalez FA, Davis RJ . Genomic loci of human mitogen-activated protein kinases . Oncogene . 9 . 2 . 647–9 . February 1994 . 8290275 .
2. Web site: Entrez Gene: MAPK4 mitogen-activated protein kinase 4.
3. Petersen M, Brodersen P, Naested H, Andreasson E, Lindhart U, Johansen B, Nielsen HB, Lacy M, Austin MJ, Parker JE, Sharma SB, Klessig DF, Martienssen R, Mattsson O, Jensen AB, Mundy J . 6 . Arabidopsis map kinase 4 negatively regulates systemic acquired resistance . Cell . 103 . 7 . 1111–20 . December 2000 . 11163186 . 10.1016/S0092-8674(00)00213-0 . 1864451 . free .
4. Wang W, Shen T, Dong B, Creighton CJ, Meng Y, Zhou W, Shi Q, Zhou H, Zhang Y, Moore DD, Yang F . 6 . MAPK4 overexpression promotes tumor progression via noncanonical activation of AKT/mTOR signaling . The Journal of Clinical Investigation . 129 . 3 . 1015–1029 . March 2019 . 30688659 . 10.1172/JCI97712 . 6391107.