INDUCERS OF THE HEAT-SHOCK RESPONSE STIMULATE PHOSPHOLIPASE-C AND PHOSPHOLIPASE-A2 ACTIVITY IN MAMMALIAN-CELLS

Although the mammalian heat shock response has been well characterized , the processes that mediate the induction of the response and the reg ulation of heat shock protein function are not completely understood. We have investigated the potential role in heat-shocked cells of phosp hoinositide-specific phospholipase C (PLC), a membrane enzyme activity involved in transmembrane signal transduction. Our studies indicate t hat heat shock activates PLC in each of seven cell lines, including ce lls of human, rat, mouse, and hamster origin. Heat shock produced incr eases in inositol phosphate concentrations comparable in magnitude to those achieved after simulation with growth factors, indicating that h eat shock might initiate transmembrane signaling cascades of potential importance in cellular regulation. Common cellular responses to heat and growth factors also included feedback modulation of PLC by its pro ducts and the parallel stimulation of phospholipase A, activity. In ad dition to heat shock, other agents that induce the stress response sti mulated PLC activity. The data indicate a close correlation between ex pression of the mammalian heat shock response and stimulation of PLC a ctivity and indicate a possible role for this enzyme activity in the r egulation of some aspects of the stress response.