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Acta
Biochim Biophys Sin 2005,37:501-505
doi:10.1111/j.1745-7270.2005.00069.x
Heat Shock Protein 90 Indirectly Regulates ERK Activity by
Affecting Raf Protein Metabolis
Fei DOU*, Liu-Di YUAN, and Jing-Jing ZHU
Department of Genetics and Development Biology, Southeast
University Medical School, Nanjing 210009, China
Abstract 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.
Key words molecular chaperone;
phosphorylation; Hsp90; extracellular signal-regulated protein kinase (ERK);
Raf; tau
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