Title: SITE SPECIFIC PHOSPHORYLATION OF HEAT SHOCK PROTEIN 27 (HSP27) REGULATES CELL SURVIVAL AND DEATH
Abstract: Hsp27 is constitutively expressed and increases in response to stress. Pretreatment of LLC‐PK1 cells with 11‐deoxy‐16,16‐dimethyl PGE 2 (DDM‐PGE 2 ) selectively increases constitutive Hsp27 expression and contributes to protection against 2,3,5‐ tris (glutathion‐ S ‐yl)hydroquinone (TGHQ) induced cytotoxicity. We have now identified specific changes in Hsp27 phosphorylation during DDM‐PGE 2 mediated cytoprotection. 2D gel electrophoresis revealed that in addition to constitutive pS 15 ‐Hsp27, TGHQ induces the formation of 2 additional Hsp27‐positive proteins. 2D western analysis subsequently identified TGHQ induced pS 84 ‐ and pS 88 ‐Hsp27, both of which are translocated to the nucleus. Pretreatment of LLC‐PK1 cells with DDM‐PGE 2 increases the constitutive expression of pS 15 ‐Hsp27 in the cytosol and the nucleus, and specifically decreased TGHQ‐mediated induction of pS 84 ‐Hsp27. These findings were confirmed by mass spectrometric analysis. Interestingly, although the inhibition of p38 MAPK prevented TGHQ‐induced pS 84 ‐Hsp27 phosphorylation and cytotoxicity, transfection of cells with mutant Hsp27 (S 15,84,88 → A 15,84,88 ) or p‐Hsp27 (S 15,84,88 →D 15,84,88 ) had no effect on TGHQ‐induced cytotoxicity. The data suggest that the specific phosphorylation of Hsp27 at Ser 84 negatively regulates cell survival, and that pS 15 ‐Hsp27 may be positively associated with cell survival. (GM56321, ES06694).
Publication Year: 2008
Publication Date: 2008-03-01
Language: en
Type: article
Indexed In: ['crossref']
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