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J. Biochem, 2003, Vol. 133, No. 1 103-108
© 2003 Japanese Biochemical Society


CELL

Inhibition of Mitogen-Activated Kinase Kinase Kinase 3 Activity through Phosphorylation by the Serum- and Glucocorticoid-Induced Kinase 1

Jaesun Chun1, Taegun Kwon3, Dae Joong Kim3, Ingun Park1, Guhung Chung5, Eun Jeoung Lee1, Soon Kwang Hong4, Soo-Ik Chang2, Hack Young Kim2 and Sang Sun Kang+,1

1 School of Science Education and 2 School of Biological Science, Chungbuk National University, Chongju, 361-763, Republic of Korea; 3 Samsung Biomedical Research Institute, Seoul, 161-763, Republic of Korea; 4 Division of Life Science, Myungji University, Youngin, Kyungki do, 361-763, Republic of Korea; and 5 School of Biological Science, Seoul National University, Seoul, 151-742, Republic of Korea

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)-{phi}, where {phi} 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.

+ To whom correspondence should be addressed. Tel: +82-43-261-3278, Fax: +82-43-271-0526, E- mail: jin95324{at}cbucc.chungbuk.ac.kr


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