Ndrg4 enhances NGF-induced ERK activation uncoupled with Elk-1 activation.
Ndrg4 is expressed predominantly in the early postnatal rat brain and may be related to neural cell differentiation. PC12 cell lines stably expressing increased levels of Ndrg4 protein display enhanced NGF-induced phosphorylation of MEK and ERK. In contrast, the Ndrg4-C2-overexpressed PC12 cell lines showed attenuated NGF-promoted phosphorylation of Elk-1, which is a nuclear target of ERK. A reporter assay also indicated that Ndrg4-C2 suppresses Elk-1-mediated transcriptional activation and SRE reporter expression. The suppressive effect of Ndrg4-C2 on NGF-induced activation of Elk-1 was abolished by colchicine but not by cytochalasin D, suggesting that microtubules are involved in the reduced activation of Elk-1 by Ndrg4. Ndrg4 may play a role in supporting the activation of ERK and its target proteins needed for neuronal differentiation and in reducing the activation of Elk-1 implicated in cell growth.
Hongo
Shigeki
S
Department of Biochemistry, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8555, Japan. shongo@med.showa-u.ac.jp
Watanabe
Takuya
T
Takahashi
Keiko
K
Miyazaki
Akira
A
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D004789:Enzyme Activation / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D018390:Gene Targeting; D008870:Microtubules / Q000201:enzymology / Q000378:metabolism; D009124:Muscle Proteins / Q000502:physiology*; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D016716:PC12 Cells; D010766:Phosphorylation / Q000502:physiology; D051381:Rats; D050807:ets-Domain Protein Elk-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
C494114:Elk1 protein, rat; D009124:Muscle Proteins; C486613:Ndrg4 protein, rat; D009419:Nerve Tissue Proteins; D050807:ets-Domain Protein Elk-1; D020932:Nerve Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases