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Mol. Cell. Biol., Jan 1995, 505-516, Vol 15, No. 1
JN Lavoie, H Lambert, E Hickey, LA Weber and J Landry
Phosphorylation of heat shock protein 27 (HSP27) can modulate actin
filament dynamics in response to growth factors. During heat shock, HSP27
is phosphorylated at the same sites and by the same protein kinase as
during mitogenic stimulation. This suggests that the same function of the
protein may be activated during growth factor stimulation and the stress
response. To determine the role of HSP27 phosphorylation in the heat shock
response, several stable Chinese hamster cell lines that constitutively
express various levels of the wild-type HSP27 (HU27 cells) or a
nonphosphorylatable form of human HSP27 (HU27pm3 cells) were developed. In
contrast to HU27 cells, which showed increased survival after heat shock,
HU27pm3 cells showed only slightly enhanced survival. Evidence is presented
that stabilization of microfilaments is a major target of the protective
function of HSP27. In the HU27pm3 cells, the microfilaments were
thermosensitized compared with those in the control cells, whereas
wild-type HSP27 caused an increased stability of these structures in HU27
cells. HU27 but not HU27pm3 cells were highly resistant to cytochalasin D
treatment compared with control cells. Moreover, in cells treated with
cytochalasin D, wild-type HSP27 but not the phosphorylated form of HSP27
accelerated the reappearance of actin filaments. The mutations in human
HSP27 had no effect on heat shock-induced change in solubility and cellular
localization of the protein, indicating that phosphorylation was not
involved in these processes. However, induction of HSP27 phosphorylation by
stressing agents or mitogens caused a reduction in the multimeric size of
the wild-type protein, an effect which was not observed with the mutant
protein. We propose that early during stress, phosphorylation-induced
conformational changes in the HSP27 oligomers regulate the activity of the
protein at the level of microfilament dynamics, resulting in both enhanced
stability and accelerated recovery of the filaments. The level of
protection provided by HSP27 during heat shock may thus represent the
contribution of better maintenance of actin filament integrity to overall
cell survival.
Copyright © 1995, American Society for Microbiology
Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27
Centre de recherche en cancerologie de l'Universite Laval, L'Hotel-Dieu de Quebec, Canada.
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