The RSK factors of activating the Ras/MAPK signaling cascade

Front Biosci. 2008 May 1;13:4258-75. doi: 10.2741/3003.

Abstract

The p90 ribosomal S6 kinase (RSK) constitute a family of serine/threonine kinases activated downstream of the Ras/mitogen-activated protein kinase (MAPK) pathway. In mammals, four RSK genes have been identified (RSK1, RSK2, RSK3 and RSK4), and RSK orthologues have also been described in D. melanogaster and C. elegans, but not in yeast or plants. The RSK isoforms are composed of two distinct and functional kinase domains that are activated in a sequential manner by a series of phosphorylation events. These enzymes were among the first substrates of extracellular signal-regulated kinase (ERK) to be discovered and have proven to be ubiquitous and multifunctional mediators of ERK signal transduction. While the RSK isoforms promote cell survival though the inactivation of several apoptotic effectors, they also appear to mediate cell growth and proliferation by simultaneously regulating substrates involved in gene transcription and mRNA translation. RSK1-4 are ubiquitously expressed in cell lines and tissues, and at present, little is known about specific and overlapping functions of individual RSK isoforms. The upregulation of RSK1 and RSK2 expression in different types of cancer suggest that they may be involved in oncogenesis and could potentially be targeted in anti-cancer therapies. The recent identification of specific RSK inhibitors will likely help addressing the biological functions of the RSK isoforms and their contributions in pathological conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Division
  • Cell Nucleus / enzymology
  • Evolution, Molecular
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Profiling
  • Genes, ras*
  • Humans
  • Intracellular Space / metabolism
  • Kinetics
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / physiology*
  • Models, Biological
  • Phosphorylation
  • Ribosomal Protein S6 Kinases, 90-kDa / genetics
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism*
  • Signal Transduction

Substances

  • Ribosomal Protein S6 Kinases, 90-kDa
  • ribosomal protein S6 kinase, 90kDa, polypeptide 3
  • Extracellular Signal-Regulated MAP Kinases