Induction of in vitro differentiation of mouse embryonal carcinoma (F9) and erythroleukemia (MEL) cells by herbimycin A, an inhibitor of protein phosphorylation.

Abstract

Abstract. Herbimycin A is one of the benzenoid ansamycin antibiotics isolated from a culture of a Streptomyces species (Omura, S., A. Nakagawa, and N. Sadakane. 1979. Tetrahedron Lett. 1979 164: 294-298). These studies and other evidence indicate that the antibiotic inhibits a reaction(s) closely associated with the function of cellular tyrosine kinases.We have found that herbimycin A is an effective inducing agent capable of triggering differentiation in two typical mouse in vitro differentiation systems, which have been considered to be quite different in their mechanism of induction: endoderm differentiation of embryonal carcinoma (F9) cells and terminal erythroid differentiation of erythroleukemia (MEL) cells. The results suggest that there is a common step in the intracellular differentiation cascade which is, directly or indirectly, associated with phosphorylation at specific (tyrosine) residues of cellular proteins. The significance of this finding with respect to the molecular mechanism of in vitro differentiation is discussed.

Pamlin‐induced tyrosine phosphorylation of SUp62 protein in primary mesenchyme cells during early embryogenesis in the sea urchin, Hemicentrotus pulcherrimus

“…To examine whether this is the case, HA, a known inhibitor of non‐receptor type PTK (e.g. Honma et al 1989 ; Kondo et al 1989 ) was used to see whether PMC migration was interfered with to any extent. By treating unhatched embryos with 10 μg/mL HA for 5 h, embryos reached the early mesenchyme blastula stage.…”

Decrease in protein tyrosine phosphorylation is associated with F-actin reorganization by retinoic acid in human endometrial adenocarcinoma (RL95-2) cells

“…A number of pro- teins contribute to the multiple cytoskeletal proteins concentrated at focal adhesions (Owens et al, 1995). Focal adhesion proteins have been categorized as either structural molecules, such as the actin-binding proteins tensin and vinculin, or regulatory molecules, including focal adhesion kinase (FAK) and paxillin (Kondo et al, 1989;Wood et al, 1994). Our results demonstrated that in RL95-2 cells retinoic acid did not cause changes in phosphorylation of FAK (data not shown), a protein with a molecular weight of 125 kDa, although actin filaments were reorganized.…”

“…Enhanced activity of protein tyrosine kinases has been implicated in the establishment and progression of many cancers and other diseases (Levitzki and Gazit, 1995). Inhibition of protein tyrosine kinases causes actin filament reorganization (Kwon et al, 1995) and differentiation of erythroid, mouse embryonal carcinoma (F9) and human leukemia cells (Kondo et al, 1989;Honma et al, 1989). Tyrphostins inhibit several tyrosine kinases (Levitzki and Gazit, 1995) while inducing differentiation of mouse erythroleukemic cells (Anafi et al, 1993b).…”