Heat shock-induced actin polymerization, SAPK/JNK activation, and heat-shock protein expression are mediated by genistein-sensitive tyrosine kinase(s) in K562 cells.
Upon exposure to elevated growth temperatures, mammalian cells exhibit a variety of cellular responses, such as the expression of heat-shock proteins (HSPs) and the activation of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). In this study, we show that heat shock transiently induces morphological change (cell elongation) and polymerization of actin, but not of microtubules, in human erythroleukaemic K562 cells. Pretreatment with actinomycin D or cycloheximide did not prevent the heat shock-induced cell elongation and actin reorganization, indicating that gene transcription and protein synthesis are not required for this phenomenon. The alterations in cell morphology and actin structure in response to heat shock were specifically inhibited by genistein, a tyrosine kinase inhibitor, but not by other kinase inhibitors, including tyrosine kinase inhibitors (herbimycin and tyrphostin) and protein kinase C inhibitors (staurosporine and H7). The activities of genistein-sensitive tyrosine kinase (GTK) and c-Src were enhanced by heat-shock treatment. In addition, a 75 kDa protein was highly phosphorylated in its tyrosine residues(s) by heat shock, and the phosphorylation was prevented by genistein pretreatment. Genistein also inhibited the heat-shock-induced SAPK/JNK activation and HSP expression. In contrast, while colchicine, a microtubule-disrupting agent, was able to induce actin polymerization and SAPK/JNK activation, these events were not inhibited by genistein. These results suggest that the heat-shock-induced actin polymerization, HSP expression, and SAPK/JNK activation may be mediated by the specific signal pathway involving GTK(s), while colchicine-induced actin polymerization and SAPK/JNK activation is regulated in a different manner.