PROTEIN-KINASE INHIBITORS ABOLISH ADAPTATIVE CELL BEHAVIOR IN TETRAHYMENA

Studies on the chemosensory behaviour of the ciliated protozoan Tetrah ymena thermophila showed that protein kinase inhibitors abolish the ad aptative swimming behaviour of the cells by making them unable to resp ond to a chemoattractant. Using proteose peptone or insulin as chemoat tractants, dose/response-curves could be constructed for a number of t yrosine kinase inhibitors leading to complete inhibition of chemoattra ction for genistein as well as for tyrphostin A47 (both at 80 mu M) wh ereas the negative control substances daidzein and tyrphostin A63, use d at the same concentrations, had no effects when the chemosensory beh aviour was measured by a two-phase assay for chemoattraction. The more general protein kinase inhibitor staurosporine used at 30 nM was also inhibiting adaptative cell behaviour. Measurements of swimming speeds of individual cells by video-microscopy showed, in general, a stimula tory effect on swimming rates at the same concentrations of inhibitors when an inhibition was observed of the adaptation process. The result s suggest that phosporylation of amino acid residues in proteins is a crucial step in adaptative swimming behaviour leading to chemoattracti on. The abolishment of adaptation by inhibitors of protein kinases is possibly due to an inhibitory effect on ciliary reversals as more pers istent forward swimming was observed in the presence of these inhibito rs.