herbimycin and Pheochromocytoma

An involvement of protein tyrosine kinase in the transduction of the signals initiated by nerve growth factor (NGF) was investigated. A tyrosine kinase inhibitor, herbimycin, inhibited neurite outgrowth of rat pheochromocytoma PC12 cells induced by NGF but not that by dibutyryl-cAMP. Herbimycin and genistein blocked NGF-dependent activation of ras p21 whose essential function in neuronal differentiation has been reported. These observations suggested that tyrosine kinase activity is involved in the signaling pathways. K-252a, by contrast, inhibited NGF-induced but not EGF-dependent activation of ras p21. Tyrosine kinase activity of gp140trk, a constituent of NGF receptor, is activated by NGF for much a longer period compared to the activation of EGF receptor autokinase activity by EGF. We further demonstrated that autophosphorylation of gp140trk is selectively inhibited by K-252a.

Topics: Adrenal Gland Neoplasms; Amino Acid Sequence; Animals; Benzoquinones; Bucladesine; Carbazoles; Glycoproteins; Indole Alkaloids; Lactams, Macrocyclic; Molecular Sequence Data; Nerve Growth Factors; Oncogene Protein p21(ras); Pheochromocytoma; Phosphorylation; Protein-Tyrosine Kinases; Quinones; Rats; Receptors, Cell Surface; Receptors, Nerve Growth Factor; Rifabutin; Signal Transduction; Tumor Cells, Cultured