Open AccessHeat Shock Protein 90 Indirectly Regulates ERK Activity by Affecting Raf Protein Metabolism
Author(s) -
DOU Fei,
YUAN LiuDi,
ZHU JingJing
Publication year - 2005
Publication title -
acta biochimica et biophysica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.771
H-Index - 57
eISSN - 1745-7270
pISSN - 1672-9145
DOI - 10.1111/j.1745-7270.2005.00069.x
Subject(s) - mapk/erk pathway , kinase , hsp90 , microbiology and biotechnology , heat shock protein , protein kinase a , phosphorylation , extracellular , chemistry , biology , biochemistry , gene
Extracellular signal‐regulated protein kinase (ERK) has been implicated in the pathogenesis of several nerve system diseases. As more and more kinases have been discovered to be the client proteins of the molecular chaperone Hsp90, the use of Hsp90 inhibitors to reduce abnormal kinase activity is a new treatment strategy for nerve system diseases. This study investigated the regulation of the ERK pathway by Hsp90. We showed that Hsp90 inhibitors reduce ERK phosphorylation without affecting the total ERK protein level. Further investigation showed that Raf, the upstream kinase in the Ras‐Raf‐MEK‐ERK pathway, forms a complex with Hsp90 and Hsp70. Treating cells with Hsp90 inhibitors facilitates Raf degradation, thereby down‐regulating the activity of ERK. Edited by Ke‐Yi WANG