Kinase Subfamily ERK7

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Kinase Classification: Group Atypical: Family MAPK: Subfamily ERK7

ERK7 (Extracellular signal Regulated Kinase) is an ancient but poorly studied member of the MAPK family, found in almost all eukaryotes other than fungi and plants. Like most other MAPKs it has a T[DE]Y motif in its activation loop, and both residues are seen to be phosphorylated in the human protein (Phosphosite). These residues in most MAPK are phosphorylated by a MEK (MAP2K) kinase, but for human Erk7, it may autophosphorylate: protein produced in E. coli was dual-phosphorylated, while catalytically-dead mutants of Erk7 were not phosphorylated in human cells under conditions where the wild type was phosphorylated and active. [1]


Evolution

Erk7 is found in almost all eukaryotes other than fungi and plants. In several protist lineages it is the only MAPK other than Erk1. Most animals have a single copy of Erk7.


Control of activity

In human, one paper shows that the tyrosine kinases Ret and Abl may lie indirectly upstream of Erk7 [2]

Domain Structure

All Erk7 have an N-terminal kinase domain, followed immediately by a unique conserved region of about 45 AA and then usually an extended and relatively poorly conserved C-terminal tail.

The C-terminal region mediates nuclear localization, activation, and... ...


A small-scale RNAi screen in Trypansoma brucei showed Erk7 (Erk8) to be required for normal proliferation. [3]. A pair of RNAi screens in Drosophila S2 cells also reported that CG32703 is required for cell cycle progression [4, 5].

The Dictyostelium homolog, erkB (erk2) is activated in response either to cAMP (induces chemotaxis and development) or folate (induces chemotaxis and feeding). [6] The cAMP signal is thought to be mediated by a direct interaction between a G-alpha protein and Erk2 [7], though this is may not be absolutely required [], and erkB is required to produce further cAMP in response to the cAMP signal. erkB may act through docking and phosphorylating REGA, a cAMP-specific phosphodiesterase


References

  1. Klevernic IV, Stafford MJ, Morrice N, Peggie M, Morton S, and Cohen P. Characterization of the reversible phosphorylation and activation of ERK8. Biochem J. 2006 Feb 15;394(Pt 1):365-73. DOI:10.1042/BJ20051288 | PubMed ID:16336213 | HubMed [Klevernic]
  2. Iavarone C, Acunzo M, Carlomagno F, Catania A, Melillo RM, Carlomagno SM, Santoro M, and Chiariello M. Activation of the Erk8 mitogen-activated protein (MAP) kinase by RET/PTC3, a constitutively active form of the RET proto-oncogene. J Biol Chem. 2006 Apr 14;281(15):10567-76. DOI:10.1074/jbc.M513397200 | PubMed ID:16484222 | HubMed [Iavarone]
  3. pmid= 21668652 [Mackey]
  4. Bettencourt-Dias M, Giet R, Sinka R, Mazumdar A, Lock WG, Balloux F, Zafiropoulos PJ, Yamaguchi S, Winter S, Carthew RW, Cooper M, Jones D, Frenz L, and Glover DM. Genome-wide survey of protein kinases required for cell cycle progression. Nature. 2004 Dec 23;432(7020):980-7. DOI:10.1038/nature03160 | PubMed ID:15616552 | HubMed [Bettencourt-Dias]
  5. Björklund M, Taipale M, Varjosalo M, Saharinen J, Lahdenperä J, and Taipale J. Identification of pathways regulating cell size and cell-cycle progression by RNAi. Nature. 2006 Feb 23;439(7079):1009-13. DOI:10.1038/nature04469 | PubMed ID:16496002 | HubMed [Bjorklund]
  6. Hadwiger JA and Nguyen HN. MAPKs in development: insights from Dictyostelium signaling pathways. Biomol Concepts. 2011 Apr 1;2(1-2):39-46. DOI:10.1515/BMC.2011.004 | PubMed ID:21666837 | HubMed [Hadwiger]
  7. Nguyen HN and Hadwiger JA. The Galpha4 G protein subunit interacts with the MAP kinase ERK2 using a D-motif that regulates developmental morphogenesis in Dictyostelium. Dev Biol. 2009 Nov 15;335(2):385-95. DOI:10.1016/j.ydbio.2009.09.011 | PubMed ID:19765570 | HubMed [Nguyen]
All Medline abstracts: PubMed | HubMed