Inhibition of ret tyrosine kinase activity by herbimycin A.
We examined the effect of herbimycin A, a potent inhibitor of tyrosine kinases, on NIH(ret) cells and TPC-1 papillary thyroid carcinoma cells, both of which express the active ret genes. Herbimycin A reversed the morphology of NIH(ret) cells to flat cells with a concomitant reassembly of microfilament bundles. On the other hand, it did not induce a significant change in cell shape of TPC-1 cells. When tyrosine kinase activities of the active ret gene products in herbimycin A-treated NIH(ret) and TPC-1 cells were examined in immunocomplex kinase assays, they drastically decreased in both cells as compared with untreated cells. In addition, herbimycin A strongly inhibited tyrosine phosphorylation of 40 kDa and 31 kDa proteins present in the immunoprecipitates of both cells, suggesting that these proteins could associate with the Ret proteins.
Taniguchi
M
M
Department of Pathology, Nagoya University School of Medicine, Japan.
Uehara
Y
Y
Matsuyama
M
M
Takahashi
M
M
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000596:Amino Acids / Q000032:analysis; D016227:Benzoquinones; D002460:Cell Line; D029721:Drosophila Proteins; D006801:Humans; D047029:Lactams, Macrocyclic; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes; D011809:Quinones / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases; D017828:Rifabutin / Q000031:analogs & derivatives; D013964:Thyroid Neoplasms; D014407:Tumor Cells, Cultured
D000199:Actins; D000596:Amino Acids; D016227:Benzoquinones; D029721:Drosophila Proteins; D047029:Lactams, Macrocyclic; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila