Nemo-like kinase, an essential effector of anterior formation, functions downstream of p38 mitogen-activated protein kinase.
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 p38beta 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 p38alpha, 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 p38beta expression could be rescued by expression of wild-type NLK but not by expression of mutant NLK lacking the p38beta 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.
Ohnishi
Eriko
E
Department of Molecular Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan.
Goto
Toshiyasu
T
Sato
Atsushi
A
Kim
Mi-Sun
MS
Iemura
Shun-Ichiro
S
Ishitani
Tohru
T
Natsume
Tohru
T
Ohnishi
Junji
J
Shibuya
Hiroshi
H
D000818:Animals; D045744:Cell Line, Tumor; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D014981:Xenopus / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
D029867:Xenopus Proteins; D020928:Mitogen-Activated Protein Kinases; C490332:mapk14a protein, Xenopus; C462720:nemo like kinase, Xenopus; D048051:p38 Mitogen-Activated Protein Kinases