Protein kinase inhibitors can suppress stress-induced dissociation of Hsp27

Citation
K. Kato et al., Protein kinase inhibitors can suppress stress-induced dissociation of Hsp27, CELL STR CH, 6(1), 2001, pp. 16-20
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL STRESS & CHAPERONES
ISSN journal
1355-8145 → ACNP
Volume
6
Issue
1
Year of publication
2001
Pages
16 - 20
Database
ISI
SICI code
1355-8145(200101)6:1<16:PKICSS>2.0.ZU;2-X
Abstract
We previously showed that the aggregated form of Hsp27 in cultured cells be comes dissociated as a result of phosphorylation with various types of stre ss. In order to clarify the signal transduction cascade involved, the effec ts of various inhibitors of protein kinases and dithiothreitol on the disso ciation of Hsp27 were here examined by means of an immunoassay after fracti onation of cell extracts by sucrose density gradient centrifugation. The di ssociation of Hsp27 induced by exposure of U251 MG human glioma cells to me tals (NaAsO2 and CdCl2), hypertonic stress (sorbitol and NaCl), or amisomyc in, an activator of p38 mitogen-activated protein (MAP) kinase, was complet ely suppressed by the presence of SE 203580 or PD 169316, inhibitors of p38 MAP kinase, but not by PD 98059 and Uo 126, inhibitors of MAP kinase kinas e (MEK), nor by staurosporine, Go 6983, and bisindolylmaleimide I, inhibito rs of protein kinase C. Phorbol ester (PMA)-induced dissociation of Hsp27 w as completely suppressed by staurosporine, Go 6933, or bisindolylmaleimide 1 and partially suppressed by SE 203580, or PD 169316 but not by PD 98059 o r Uo 126, indicating mediation by 2 cascades. The presence of 1 mM dithioth reitol in the culture medium during exposure to chemicals suppressed the di ssociation of Hsp27 induced by arsenite and CdCl2 but not by other chemical s. These results suggest that the phosphorylation of Hsp27 is catalyzed by 2 protein kinases, p38 MAP kinase-activated protein (MAPKAP) kinase2/3 and protein kinase C. In addition, metal-induced signals are sensitive to reduc ing power.