SODIUM-BUTYRATE INDUCES TYROSINE PHOSPHORYLATION AND ACTIVATION OF MAP KINASE (ERK-1) IN HUMAN K562 CELLS

Butyrate is a naturally occuring 4-carbon fatty acid. Biologically, bu tyrate has been shown to affect the morphology and growth rate of mamm alian cells, as well as induce gene expression. Moreover, butyrate has been proven to serve as an anticancer agent, which unlike others (met hotrexate and hydroxyurea), is a nontoxic, safe alternative to cancer treatment. It also induces erythroid differentiation in K562 cells. Ho wever, its mechanism of action has yet to be determined. In this study we investigated the effects of sodium butyrate (NaB) on tyrosine phos phorylation in K562 erythroleukemic cells. We demonstrate that NaB ind uces both dose and time-dependent tyrosine phosphorylation of several proteins, the effects of which were blocked by the tyrosine kinase inh ibitor genistein. Furthermore, NaB induces tyrosine phosphorylation an d rapid activation of MAP kinase (ERK-1). These findings provide the f irst evidence that the signal transduction mechanism of NaB involves r apid tyrosine phosphorylation and activation of MAP kinase. (C) 1995 A cademic Press, Inc.