Nemo-like kinase, an essential effector of anterior formation, functions downstream of p38 mitogen-activated protein kinase

Eriko Ohnishi, Toshiyasu Goto, Atsushi Sato, Mi Sun Kim, Shun Ichiro Iemura, Tohru Ishitani, Tohru Natsume, Junji Ohnishi, Hiroshi Shibuya

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14 Citations (Scopus)

Abstract

Nemo-like kinase (NLK) is known to function as a mitogen-activated protein kinase (MAPK)-like kinase. However, the upstream molecules and molecular mechanisms that regulate NLK activity remain unclear. In the present study, we identified p38 MAPK as an upstream kinase and activator of NLK. p38 regulates the function of NLK via phosphorylation, and this modification can be abrogated by depletion of endogenous p38. In Xenopus laevis embryos, depletion of either p38β or NLK by antisense morpholino oligonucleotides results in a severe defect in anterior development and impaired expression of endogenous anterior markers. It is notable that morphants of Xenopus p38α, another isoform of the p38 MAPK family, exhibited no obvious defects in anterior development. Defects in head formation or in the expression of anterior marker genes caused by suppression of endogenous p38β expression could be rescued by expression of wild-type NLK but not by expression of mutant NLK lacking the p38β phosphorylation site. In contrast, defects in head formation or in the expression of anterior marker genes caused by suppression of endogenous NLK expression could not be rescued by expression of p38. These results provide the first evidence that p38 specifically regulates NLK function, which is required for anterior formation in Xenopus development.

Original languageEnglish
Pages (from-to)675-683
Number of pages9
JournalMolecular and cellular biology
Volume30
Issue number3
DOIs
Publication statusPublished - Feb 1 2010

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Ohnishi, E., Goto, T., Sato, A., Kim, M. S., Iemura, S. I., Ishitani, T., Natsume, T., Ohnishi, J., & Shibuya, H. (2010). Nemo-like kinase, an essential effector of anterior formation, functions downstream of p38 mitogen-activated protein kinase. Molecular and cellular biology, 30(3), 675-683. https://doi.org/10.1128/MCB.00576-09