The association of the JNK scaffold protein, WDR62, with the mixed lineage kinase 3, MLK3


Submitted: 9 June 2015
Accepted: 17 October 2015
Published: 23 October 2015
Abstract Views: 3233
PDF: 979
Appendix: 438
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Authors

  • Miriam Hadad Department of Cell Biology and Cancer Science, The B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
  • Sharon Aviram Department of Cell Biology and Cancer Science, The B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
  • Ilona Darlyuk-Saadon Department of Cell Biology and Cancer Science, The B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
  • Ksenya Cohen-Katsenelson Department of Cell Biology and Cancer Science, The B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
  • Alan J. Whitmarsh Faculty of Life Sciences, University of Manchester, Michael Smith Building, Manchester, United Kingdom.
  • Ami Aronheim Department of Cell Biology and Cancer Science, The B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Mitogen-activated protein kinases (MAPKs) form a kinase tier module in which MAPK, MAP2K and MAP3K are held by scaffold proteins. The scaffold proteins serve as a protein platform for selective and spatial kinase activation. The precise mechanism by which the scaffold proteins function has not yet been fully explained. WD40-repeat protein 62, WDR62 is a novel scaffold protein of the c-Jun N-terminal kinase (JNK) pathway. WDR62 is a 1523 a.a. long protein with no significant sequence homology to a known gene. Previously WDR62 was shown to associate with JNK and MKK4/7 in a modular fashion. Here, we show that WDR62 is able to associate with multiple members of the MAP3K of the mixed lineage kinase family and we map WDR62-MLK3 interacting domains. We identify two separable interacting domains within WDR62 and MLK3 proteins that can cross associate. MLK3 association with WDR62 is independent of JNK and MKK4/7 domains and activities. CDC42 activation disrupts WDR62-MLK3 association independent of MLK3 kinase activity.

Supporting Agencies

The Israel Science Foundation grant # 573/11 to A.A., Wellcome Trust 088232/Z/09/Z to A.J.W.

Hadad, M., Aviram, S., Darlyuk-Saadon, I., Cohen-Katsenelson, K., Whitmarsh, A. J., & Aronheim, A. (2015). The association of the JNK scaffold protein, WDR62, with the mixed lineage kinase 3, MLK3. MAP Kinase, 4(1). https://doi.org/10.4081/mk.2015.5307

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