Herbimycin A inhibits the association of p60v-src with the cytoskeletal structure and with phosphatidylinositol 3' kinase.
To search for the biochemical prerequisites for morphological transformation by p60v-src, we examined the effect of herbimycin A, a potent inhibitor of cell transformation, on chicken embryonic fibroblasts transformed by Rous sarcoma virus. A small dose of herbimycin (0.1-0.3 micrograms ml-1) was enough to convert the cell morphology to a normal phenotype with a concomitant reassembly of microfilament bundles. In the cells treated with the drug, the majority of the substrates for p60v-src remained phosphorylated and p60v-src was myristylated, membrane associated and fairly active as a protein kinase. Under the same conditions, however, the association of p60v-src with the cytoskeletal structure and with phosphatidylinositol 3' kinase was strongly inhibited, suggesting that the interactions of p60v-src with the cellular structure and the enzyme were indispensable for morphological transformation.
Nagoya University School of Medicine, Japan.
M
M
Hamaguchi
H
H
Xiao
Y
Y
Uehara
Y
Y
Ohnishi
Y
Y
Nagai
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001358:Avian Sarcoma Viruses; D016227:Benzoquinones; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D002642:Chick Embryo; D003599:Cytoskeleton / Q000378:metabolism*; D047029:Lactams, Macrocyclic; D015688:Oncogene Protein pp60(v-src) / Q000032:analysis / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D010770:Phosphotransferases; D019869:Phosphatidylinositol 3-Kinases; D015688:Oncogene Protein pp60(v-src)