Suppression of RAS and MOS transformation by radicicol.
Activated versions of ras and mos oncogenes subvert the signal transduction pathway by mimicking transducers at the plasma membrane and cytosol respectively. Radicicol (UCS1006), an antifungal antibiotic, had the ability to suppress transformation by ras and mos oncogenes in a rapid, reversible and dose-dependent manner. UCS1006 inhibited MAP kinase activity (both ERK1 and ERK2) in untransformed as well as ras and mos transformed cells. However, ERK2 but not ERK1 activity was constitutively elevated in ras and mos transformed cells used in this study. In addition, a 62 kDa (kilodalton) phosphoprotein was identified whose tyrosine phosphorylation was inhibited by UCS1006, in both ras and mos transformed cells. This 62 kDa phosphoprotein, which was found to be heavily phosphorylated on tyrosine residues only in the ras and mos transformed cells but not in untransformed NIH3T3 cells, was identical to the previously described GAP-associated tyrosine phosphoprotein, p62, that is the major target for phosphorylation in cells transformed by tyrosine kinase oncogenes. These results suggest that agents such as radicicol can suppress transformation by diverse oncogenes such as src, ras and mos at least in part by inhibiting the function of key signal transduction intermediates such as MAP kinase and GAP-associated p62.
Zhao
J F
JF
Department of Microbiology and Immunology, University of Tennessee, Memphis 38163, USA.
Nakano
H
H
Sharma
S
S
D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D020690:GTPase-Activating Proteins; D016258:Genes, mos; D011905:Genes, ras; D007783:Lactones / Q000494:pharmacology*; D018942:Macrolides; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011506:Proteins / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D007783:Lactones; D018942:Macrolides; D010750:Phosphoproteins; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C035359:monorden