Phosphatidylinositol 3-kinase Signals Activate a Selective Subset of Rac/Rho-dependent Effector Pathways

Curr Biol. 1996 Nov 1;6(11):1445-55. doi: 10.1016/s0960-9822(96)00749-x.

Abstract

Background: Phosphatidylinositol 3'-hydroxyl kinase (PI 3-kinase) is activated by many growth factor receptors and is thought to exert its cellular functions through the elevation of phosphatidylinositol (3,4,5)-triphosphate levels in the cell. PI 3-kinase is required for growth-factor induced changes of the actin cytoskeleton which are mediated by the GTPases Rac and Rho. Recently, a role for Rac and Rho in regulating gene transcription has become evident.

Results: Here, we show that membrane targeting of the p110 catalytic subunit, but not the p85 regulatory subunit, of PI 3-kinase generates a constitutively active enzyme that allows us to assess the relative contribution of PI 3-kinase activation to a particular cellular response. Expression of this active PI 3-kinase induced actin reorganization in the form of Rac-mediated lamellipodia and focal complexes, and Rho-mediated stress fibres and focal adhesions. However, expression of active PI 3-kinase did not induce the Ras/Rac/Rho signalling pathways that regulate gene transcription controlled by the c-fos promoter, the c-fos serum response element or the transcription factors Elk-1 and AP-1.

Conclusions: Our results demonstrate that PI 3-kinase induces a selective subset of cellular responses, but is not sufficient to stimulate the full repertoire of Rac- or Rho-mediated responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • CD2 Antigens / genetics
  • CD2 Antigens / metabolism
  • COS Cells
  • Cell Membrane / metabolism
  • Cytoskeleton
  • DNA
  • DNA-Binding Proteins / metabolism
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • Serum Response Factor
  • Signal Transduction / physiology*
  • Transcription Factors*
  • ets-Domain Protein Elk-1
  • rac GTP-Binding Proteins
  • rho GTP-Binding Proteins

Substances

  • CD2 Antigens
  • DNA-Binding Proteins
  • ELK1 protein, human
  • Elk1 protein, mouse
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-fos
  • Serum Response Factor
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • DNA
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • GTP-Binding Proteins
  • rac GTP-Binding Proteins
  • rho GTP-Binding Proteins

Associated data

  • GENBANK/X05111
  • GENBANK/X12566