Delay in serum stimulation of Erk activity caused by oncogenic transformation.
Mitogenic growth factor stimulation activates several signal transduction pathways, including the well-characterized Ras-Erk pathway, resulting in transient activation of Erk1 and Erk2. Oncogenic transformation, however, causes constitutive activation of growth signalling pathways, resulting in an accelerated rate of cell division. We investigated the effects of transformation on serum and growth factor stimulation of Erk1 and Erk2, and show that stimulation of these MAP kinases, as well as the Erk activator Mek, is delayed in oncogene transformed cells. Possible mechanisms of this delay are explored. In addition, our data indicate that prolonged mitogenic stimulation does not necessarily result in constitutive activation of Erk1 and Erk2.
Greulich
H
H
Laboratory of Molecular Oncology, Rockefeller University, New York, NY 10021, USA.
Reichman
C
C
Hanafusa
H
H
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo; D016895:Culture Media, Serum-Free; D054638:Dual Specificity Phosphatase 1; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics*; D066246:ErbB Receptors / Q000378:metabolism; D005347:Fibroblasts; D011905:Genes, ras; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009154:Mutation; D050736:Oncogene Protein v-crk; D010749:Phosphoprotein Phosphatases; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics; D015398:Signal Transduction; D013997:Time Factors
D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free; D017874:Immediate-Early Proteins; D050736:Oncogene Protein v-crk; D015682:Retroviridae Proteins, Oncogenic; D011494:Protein Kinases; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases