Inhibition of Mitogen-Activated Kinase Kinase Kinase 3 Activity through Phosphorylation by the Serum- and Glucocorticoid-Induced Kinase 1
- 1 January 2003
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journal of Biochemistry
- Vol. 133 (1) , 103-108
- https://doi.org/10.1093/jb/mvg010
Abstract
The mitogen-activated protein kinase kinase kinase 3 (MEKK3) is a member of the MAP kinase family whose cellular activity is elevated in response to growth factors, oxidative stress, and hyperosmolar conditions. MEKK3 regulates MKK3 and MKK5/6/7. MEKK3 is involved distinctively in the signal pathway for blocking cell proliferation and cell cycle progression, contradictory to the biological responses commonly associated with other members of MEKKs. Based information concerning the substrate specificity of serum- and glucocorticoid-induced kinase 1 (SGK1), R-x-R-x-x-(S/T)-ϕ, where ϕ indicates a hydrophobic amino acid, two putative phosphorylation sites (Ser166 and Ser337) were found in MEKK3. It was shown that the recombinant MEKK3 protein and fluorescein-labeled MEKK3 peptides (FITC-159epRsRhlSVi168 and FITC-330dpRgRlpSAd339) are phosphorylated by SGK1 in vitro. It was also observed that the intrinsic kinase activity of MEKK3 on Ser189 of MKK3 (equivalent to Ser207 of MKK6) decreased along with phosphorylation of Ser166 and Ser337 in MEKK3 in vitro and in vivo. Therefore, it is suggested that SGK1 inhibits MEKK3-MKK3/6 signal transduction by phosphorylation of MEKK3.Keywords
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