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- Title
Regulation of elongation factor 2 kinase by p90<sup>RSK1</sup> and p70 S6 kinase.
- Authors
Wang, Xuemin; Li, Wei; Williams, Michayla; Terada, Naohiro; Ralessi, Dario; Proud, Christopher G.
- Abstract
Elongation factor 2 kinase (eEF2k) phosphorylates and inactivates eEF2. Insulin induces dephosphorylation of eEF2 and inactivation of eEF2 kinase, and these effects are blocked by rapamycin, which inhibits the mammalian target of rapamycin, mTOR. However, the signalling mechanisms underlying these effects are unknown. Regulation of eEF2 phosphoryl- ation and eEF2k activity is lost in cells in which phosphoinositide-dependent kinase 1 (PDK1) has been genetically knocked out. This is not due to toss of mTOR function since phosphorylation of another target of mTOR, initiation factor 4E-binding protein 1, is not defective. PDK1 is required for activation of members of the AGC kinase family; we show that two such kinases, p70 S6 kinase (regulated via mTOR) and p90RSK1 (activated by Erk), phosphorylate eEF2k at a conserved serine and inhibit its activity. In response to insulin-like growth factor 1, which activates p70 S6 kinase but not Erk, regulation of eEF2 is blocked by rapamycin. In contrast, regulation of eEF2 by stimuli that activate Erk is insensitive to rapamycin, but blocked by inhibitors of MEK/Erk signalling, consistent with the involvement of p90RSK1.
- Publication
EMBO Journal, 2001, Vol 20, Issue 16, p4370
- ISSN
0261-4189
- Publication type
Academic Journal
- DOI
10.1093/emboj/20.16.4370