Regulation of elongation factor-2 kinase by pH

Maxim V. Dorovkov, Karen S. Pavur, Alexey N. Petrov, Alexey G. Ryazanov

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Elongation factor-2 kinase (eEF-2K) is a Ca2+/calmodulin-dependent protein kinase that phosphorylates and inactivates eEF-2 and that can regulate the rate of protein synthesis at the elongation stage. Here we report that a slight decrease in pH, within the range observed in vivo, leads to a dramatic activation of eEF-2K. The activity of eEF-2K in mouse liver extracts, as well as the activity of purified recombinant human eEF-2K, is low at pH 7.2-7.4 and is increased by severalfold when the pH drops to 6.6-6.8. eEF-2K requires calmodulin for activity at neutral as well as acidic pH. Kinetic studies demonstrate that the pH does not affect the KM for ATP or eEF-2 and activation of eEF-2K at acidic pH is due to an increase in Vmax. To analyze the potential role of eEF-2K in regulating protein synthesis by pH, we constructed a mouse fibroblast cell line that expresses eEF-2K in a tetracycline-regulated manner. Overexpression of eEF-2K led to a decreased rate of protein synthesis at acidic pH, but not at neutral pH. Our results suggest that pH-dependent activation of eEF-2K may play a role in the global inhibition of protein synthesis during tissue acidosis, which accompanies such processes as hypoxia and ischemia.

Original languageEnglish (US)
Pages (from-to)13444-13450
Number of pages7
JournalBiochemistry
Volume41
Issue number45
DOIs
StatePublished - Nov 12 2002

All Science Journal Classification (ASJC) codes

  • Biochemistry

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