Back to Search
Start Over
Protein Kinase C Phosphorylates Ribosomal Protein S6 Kinase βII and Regulates Its Subcellular Localization
- Source :
- Molecular and Cellular Biology. 23:852-863
- Publication Year :
- 2003
- Publisher :
- Informa UK Limited, 2003.
-
Abstract
- The ribosomal protein S6 kinase (S6K) belongs to the AGC family of Ser/Thr kinases and is known to be involved in the regulation of protein synthesis and the G(1)/S transition of the cell cycle. There are two forms of S6K, termed S6Kalpha and S6Kbeta, which have cytoplasmic and nuclear splice variants. Nucleocytoplasmic shuttling has been recently proposed for S6Kalpha, based on the use of the nuclear export inhibitor, leptomycin B. However, the molecular mechanisms regulating subcellular localization of S6Ks in response to mitogenic stimuli remain to be elucidated. Here we present data on the in vitro and in vivo phosphorylation of S6Kbeta, but not S6Kalpha, by protein kinase C (PKC). The site of phosphorylation was identified as S486, which is located within the C-terminal nuclear localization signal. Mutational analysis and the use of phosphospecific antibodies provided evidence that PKC-mediated phosphorylation at S486 does not affect S6K activity but eliminates the function of its nuclear localization signal and causes retention of an activated form of the kinase in the cytoplasm. Taken together, this study uncovers a novel mechanism for the regulation of nucleocytoplasmic shuttling of S6KbetaII by PKC-mediated phosphorylation.
- Subjects :
- Molecular Sequence Data
Active Transport, Cell Nucleus
P70-S6 Kinase 1
In Vitro Techniques
Mitogen-activated protein kinase kinase
Biology
Transfection
Cell Line
MAP2K7
Phenylephrine
Humans
Insulin
ASK1
Amino Acid Sequence
Phosphorylation
Protein kinase A
Cell Growth and Development
Molecular Biology
Protein Kinase C
Binding Sites
MAP kinase kinase kinase
Cyclin-dependent kinase 2
Ribosomal Protein S6 Kinases, 70-kDa
Cell Biology
Recombinant Proteins
Cell biology
Isoenzymes
Biochemistry
Fatty Acids, Unsaturated
biology.protein
Tetradecanoylphorbol Acetate
Cyclin-dependent kinase 9
Mitogens
Signal Transduction
Subcellular Fractions
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Biology
- Accession number :
- edsair.doi.dedup.....93b4177fe6ce11b9f5baac419838e464