Treatments of Chinese hamster fibroblasts with A23187, 2-deoxyglucose, tunicamycin, beta-mercaptoethanol or glucosamine induce an increase in cell resistance to doxorubicin and VM-26 that attains a maximum after 8 h of treatment. We tested the possibility that HSP27, a heat shock protein whose overexpression in cells was shown to confer thermoresistance and chemoresistance, might also be associated with this acquisition of drug resistance. [H-3]leucine incorporation and immunoblot analyses showed that the increased resistance was not accompanied by the synthesis or accumulation of HSP27 or other heat shock proteins. However, drug resistance promoting agents all stimulated protein kinase activities that phosphorylated HSP27 in vitro and stimulated incorporation of P-32 into HSP27 in vivo. HSP27 is thought to exert in unstressed cells functions linked with growth signal pathways. It is suggested that stimulation of HSP27 phosphorylation may modulate a protective function associated with the maintenance of signal transduction homeostasis.

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