alpha-Thrombin activates Akt via a nonreceptor tyrosine kinase in IIC9 cells.
Previous data from our laboratory show that PI 3-kinase is required for alpha-thrombin-stimulated G(1) progression in IIC9 cells. In IIC9 cells, PI 3-kinase acts downstream of Ras to activate Akt, in a pathway parallel to ERK1. Here we show that alpha-thrombin does not transactivate either the EGF receptor or the PDGF receptor as measured by tyrosine phosphorylation, suggesting that activation of PI 3-kinase by alpha-thrombin is not the result of an RTK. Interestingly, both genistein and PP1 block alpha-thrombin-stimulated Akt phosphorylation, suggesting the involvement of a member of the Src family of nonreceptor tyrosine kinases.
Phillips-Mason
Polly J
PJ
Departments of Cell and Molecular Biology, and Pharmacological and Physiological Sciences, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA.
Goel
Reema
R
Baldassare
Joseph J
JJ
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000235:genetics; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics; D013917:Thrombin / Q000502:physiology*; D015533:Transcriptional Activation
D066246:ErbB Receptors; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D017479:Receptors, Platelet-Derived Growth Factor; D013917:Thrombin