3r63

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3r63, resolution 1.70Å ()
Gene: Mapk1, Erk2, Mapk, Prkm1 (Rattus norvegicus)
Activity: Mitogen-activated protein kinase, with EC number 2.7.11.24
Related: 1erk


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

Structure of ERK2 (SPE) mutant (S246E)

Publication Abstract from PubMed

The extracellular signal-regulated kinases (ERK) 1 and 2 (ERK1/2) are members of the mitogen-activated protein kinase [MAPK] family. Upon stimulation, these kinases translocate from the cytoplasm to the nucleus, where they induce physiological processes such as proliferation and differentiation. The mechanism of translocation of this kinase involves phosphorylation of two Ser residues within a nuclear translocation signal (NTS), which allows binding to importin7 and a subsequent penetration via nuclear pores. Here we show that the phosphorylation of both Ser residues is mediated mainly by casein kinase 2 (CK2) and that active ERK may assist in the phosphorylation of the N-terminal Ser. We also demonstrate that the phosphorylation is dependent on the release of ERK from cytoplasmic anchoring proteins. Crystal structure of the phosphomimetic ERK revealed that the NTS phosphorylation creates an acidic patch in ERK. Our model is that in resting cells ERK is bound to cytoplasmic anchors, which prevent its NTS phosphorylation. Upon stimulation, phosphorylation of the ERK TEY domain releases ERK and allows phosphorylation of its NTS by CK2 and active ERK to generate a negatively charged patch in ERK, binding to importin 7 and nuclear translocation. These results provide an important role of CK2 in regulating nuclear ERK activities.

Nuclear extracellular signal-regulated kinase 1 and 2 translocation is mediated by casein kinase 2 and accelerated by autophosphorylation., Plotnikov A, Chuderland D, Karamansha Y, Livnah O, Seger R, Mol Cell Biol. 2011 Sep;31(17):3515-30. Epub 2011 Jul 5. PMID:21730285

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

3r63 is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA.

See Also

Reference

  • Plotnikov A, Chuderland D, Karamansha Y, Livnah O, Seger R. Nuclear extracellular signal-regulated kinase 1 and 2 translocation is mediated by casein kinase 2 and accelerated by autophosphorylation. Mol Cell Biol. 2011 Sep;31(17):3515-30. Epub 2011 Jul 5. PMID:21730285 doi:10.1128/MCB.05424-11

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