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A conserved docking motif in MAP kinases common to substrates, activators and regulators

Nature Cell Biology volume 2, pages 110–116 (2000)Cite this article

Abstract

Mitogen-activated protein kinases (MAPKs) are specifically phosphorylated and activated by the MAPK kinases, phosphorylate various targets such as MAPK-activated protein kinases and transcription factors, and are inactivated by specific phosphatases. Recently, docking interactions via the non-catalytic regions of MAPKs have been suggested to be important in regulating these reactions. Here we identify docking sites in MAPKs and in MAPK-interacting enzymes. A docking domain in extracellular-signal-regulated kinase (ERK), a MAPK, serves as a common site for binding to the MAPK kinase MEK1, the MAPK-activated protein kinase MNK1 and the MAPK phosphatase MKP3. Two aspartic acids in this domain are essential for docking, one of which is mutated in the sevenmaker mutant of Drosophila ERK/Rolled. A corresponding domain in the MAPKs p38 and JNK/SAPK also serves as a common docking site for their MEKs, MAPK-activated protein kinases and MKPs. These docking interactions increase the efficiency of the enzymatic reactions. These findings reveal a hitherto unidentified docking motif in MAPKs that is used in common for recognition of their activators, substrates and regulators.

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Figure 1: The CD domains in the three-dimensional structures of ERK2 and p38α.
Figure 2: Docking of ERK2 to MEK1, MKP3 and MNK1.
Figure 3: The direct binding of the CD domain to MAPK-docking sites.
Figure 4: Docking interactions increase the efficiency of enzymatic reactions.
Figure 5: Identification of the CD domain in p38 and JNK.
Figure 6: The CD domain of the MAPK family.

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Acknowledgements

We are grateful to R. Fukunaga, S. Arkinstall and M. McMahon for providing us with MNK1, MKP3 and ΔB-Raf:ER cells, respectively; M. Mishima for helpful discussion; and H. Yamanaka and R. Maeda for technical support. M.A. and T.M. are Research Fellows of the Japan Society for the Promotion of Science. This work was supported by grants from the Ministry of Education, Science and Culture of Japan (to E.N.).

Correspondence and requests for materials should be addressed to E.N.

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  1. Takuji Tanoue and Makoto Adachi: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan

    Takuji Tanoue, Makoto Adachi, Tetsuo Moriguchi & Eisuke Nishida

  2. Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, 606-8502 , Japan

    Eisuke Nishida

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Correspondence to Eisuke Nishida.

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Tanoue, T., Adachi, M., Moriguchi, T. et al. A conserved docking motif in MAP kinases common to substrates, activators and regulators. Nat Cell Biol 2, 110–116 (2000). https://doi.org/10.1038/35000065

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