The 70 kDa S6 kinase complexes with and is activated by the Rho family G proteins Cdc42 and Rac1

Cell. 1996 May 17;85(4):573-83. doi: 10.1016/s0092-8674(00)81257-x.

Abstract

The 70 kDa ribosomol S6 kinase (pp70S6k) plays an important role in the progression of cells through G1 phase of the cell cycle. However, little is known of the signaling molecules that mediate its activation. We demonstrate that Rho family G proteins regulate pp70S6k activity in vivo. Activated alleles of Cdc42 and Rac1, but not RhoA, stimulate pp70S6k activity in multiple cell types. Activation requires an intact effector domain and isoprenylation of Cdc42 and Rac1. Coexpression of Dbl, an exchange factor for Cdc42, also activates pp70S6k. Growth factor-induced activation of pp70S6k is abrogated by dominant negative alleles of Cdc42 and Rac1. In addition, Cdc42 and Rac1 form GTP-dependent complex with the catalytically inactive form of pp70S6k in vitro and in vivo, suggesting a mechanism by which these G proteins activate pp70S6k.

Publication types

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

MeSH terms

  • 3T3 Cells / cytology
  • 3T3 Cells / enzymology
  • Alleles
  • Androstadienes / pharmacology
  • Animals
  • Antifungal Agents / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Toxins*
  • Calcium-Calmodulin-Dependent Protein Kinases / physiology
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Epidermal Growth Factor / antagonists & inhibitors
  • Escherichia coli Proteins*
  • GTP Phosphohydrolases / antagonists & inhibitors
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Proteins / antagonists & inhibitors
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism
  • GTP-Binding Proteins / physiology
  • Gene Expression / physiology
  • Growth Substances / physiology
  • Guanine Nucleotide Exchange Factors
  • Guanine Nucleotides / metabolism
  • Guanosine Triphosphate / metabolism
  • Isomerism
  • JNK Mitogen-Activated Protein Kinases
  • Membrane Proteins*
  • Mice
  • Mitogen-Activated Protein Kinases*
  • Mutation / physiology
  • Phosphatidylinositol 3-Kinases
  • Phosphorylation
  • Phosphotransferases (Alcohol Group Acceptor) / physiology
  • Plant Proteins / antagonists & inhibitors
  • Plant Proteins / genetics
  • Plant Proteins / metabolism
  • Platelet-Derived Growth Factor / antagonists & inhibitors
  • Polyenes / pharmacology
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism*
  • Retroviridae Proteins, Oncogenic / genetics
  • Ribosomal Protein S6 Kinases
  • Signal Transduction / physiology
  • Sirolimus
  • Wortmannin
  • cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
  • p38 Mitogen-Activated Protein Kinases
  • rac GTP-Binding Proteins
  • rhoA GTP-Binding Protein

Substances

  • Androstadienes
  • Antifungal Agents
  • Bacterial Proteins
  • Bacterial Toxins
  • Cell Cycle Proteins
  • Escherichia coli Proteins
  • Growth Substances
  • Guanine Nucleotide Exchange Factors
  • Guanine Nucleotides
  • Mcf2 protein, mouse
  • Membrane Proteins
  • Plant Proteins
  • Platelet-Derived Growth Factor
  • Polyenes
  • Retroviridae Proteins, Oncogenic
  • HokC protein, E coli
  • Epidermal Growth Factor
  • Guanosine Triphosphate
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Protein-Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
  • rac GTP-Binding Proteins
  • rhoA GTP-Binding Protein
  • Sirolimus
  • Wortmannin