Inhibition of ERK-MAP kinase signaling by RSK during Drosophila development. Academic Article uri icon

Overview

abstract

  • Although p90 ribosomal S6 kinase (RSK) is known as an important downstream effector of the ribosomal protein S6 kinase/extracellular signal-regulated kinase (Ras/ERK) pathway, its endogenous role, and precise molecular function remain unclear. Using gain-of-function and null mutants of RSK, its physiological role was successfully characterized in Drosophila. Surprisingly, RSK-null mutants were viable, but exhibited developmental abnormalities related to an enhanced ERK-dependent cellular differentiation such as ectopic photoreceptor- and vein-cell formation. Conversely, overexpression of RSK dramatically suppressed the ERK-dependent differentiation, which was further augmented by mutations in the Ras/ERK pathway. Consistent with these physiological phenotypes, RSK negatively regulated ERK-mediated developmental processes and gene expressions by blocking the nuclear localization of ERK in a kinase activity-independent manner. In addition, we further demonstrated that the RSK-dependent inhibition of ERK nuclear migration is mediated by the physical association between ERK and RSK. Collectively, our study reveals a novel regulatory mechanism of the Ras/ERK pathway by RSK, which negatively regulates ERK activity by acting as a cytoplasmic anchor in Drosophila.

publication date

  • June 8, 2006

Research

keywords

  • Drosophila
  • Extracellular Signal-Regulated MAP Kinases
  • Ribosomal Protein S6 Kinases, 90-kDa

Identity

PubMed Central ID

  • PMC1500987

Scopus Document Identifier

  • 33746322707

Digital Object Identifier (DOI)

  • 10.1038/sj.emboj.7601180

PubMed ID

  • 16763554

Additional Document Info

volume

  • 25

issue

  • 13