Insulin-stimulated MAP-2 kinase phosphorylates and activates ribosomal protein S6 kinase II

Nature. 1988 Aug 25;334(6184):715-8. doi: 10.1038/334715a0.


Ribosomal protein S6 is a component of the eukaryotic 40S ribosomal subunit that becomes phosphorylated on multiple serine residues in response to a variety of mitogens, including insulin, growth factors, and transforming proteins of many oncogenic viruses. Recently, an activated S6 kinase (S6 K II) has been purified to homogeneity from Xenopus eggs, and characterized immunologically and at the molecular level. Purified S6 K II can be deactivated in vitro by incubation with either protein phosphatase 1 or protein phosphatase 2A. Reactivation and phosphorylation of S6 K II occurs in vitro with an insulin-stimulated microtubule-associated protein-2 (MAP-2) protein kinase which is itself a phosphoprotein that can be deactivated by protein phosphatase 2A. These studies suggest that a step in insulin signalling involves sequential activation by phosphorylation of at least two serine/threonine protein kinases.

Publication types

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

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Line
  • Enzyme Activation / drug effects
  • Female
  • Insulin / pharmacology*
  • Oocytes / enzymology
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Protein Phosphatase 1
  • Protein Phosphatase 2
  • Ribosomal Protein S6 Kinases
  • Xenopus


  • Insulin
  • Protein Kinases
  • Ribosomal Protein S6 Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1
  • Protein Phosphatase 2