Induction of the mitogen-activated protein kinase phosphatase MKP3 by nerve growth factor in differentiating PC12

60Citations
Citations of this article
18Readers
Mendeley users who have this article in their library.

Abstract

In PC12 sympathetic neurons activation and nuclear translocation of ERK family MAP kinases plays an essential role in processes underlying nerve growth factor (NGF)-dependent differentiation. We have recently cloned MKP-3 as a novel dual specificity phosphatase displaying selectivity towards inactivation of the ERK1 and ERK2 MAP kinases. Here we report that in PC12 cells, MKP-3 undergoes powerful and specific up-regulation by NGF while a number of mitogens and cellular stresses are ineffective. NGF-stimulated MKP-3 expression appears after 1 h, is maximal at 3 h, and is sustained for 5 days. This coincides with a critical period of neurite outgrowth and terminal differentiation. Consistent with a role mediating inhibition of PC12 cell MAP kinases, NGF-stimulated ERK2 activation was suppressed considerably following pretreatment with fibroblast growth factor and 9-cis-retinal, two additional differentiation factors found to induce powerfully MKP-3 expression. Given the clear cytosolic localization of MKP-3 in PC12 cells and sympathetic neurons, these results suggest a critical role for inactivating ERK MAP kinases in nonnuclear compartments during essential stages of NGF-mediated PC12 differentiation.

Cite

CITATION STYLE

APA

Camps, M., Chabert, C., Muda, M., Boschert, U., Gillieron, C., & Arkinstall, S. (1998). Induction of the mitogen-activated protein kinase phosphatase MKP3 by nerve growth factor in differentiating PC12. FEBS Letters, 425(2), 271–276. https://doi.org/10.1016/S0014-5793(98)00250-6

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free