Phosphatidylinositol 3-kinase signals activate a selective subset of Rac/Rho-dependent effector pathways.
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.
Reif
K
K
Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, London, UK. reif@icrf.icnet.uk
Nobes
C D
CD
Thomas
G
G
Hall
A
A
Cantrell
D A
DA
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D018801:CD2 Antigens / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D026362:Serum Response Factor; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins
D018801:CD2 Antigens; D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; C494113:Elk1 protein, mouse; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D026362:Serum Response Factor; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins