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S6k  -  RPS6-p70-protein kinase

Drosophila melanogaster

Synonyms: 10539, 7084, CG10539, DS6K, Dmel\CG10539, ...
 
 
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Disease relevance of S6k

 

Psychiatry related information on S6k

 

High impact information on S6k

  • Drosophila S6 kinase: a regulator of cell size [2].
  • Growth inhibition is associated with a reduction in S6K but not PKB/Akt activity [3].
  • In Drosophila, the insulin receptor/TOR/S6K signaling network plays a fundamental role in the control of metabolism and cell growth [3].
  • The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila [3].
  • Rheb is an essential regulator of S6K in controlling cell growth in Drosophila [4].
 

Biological context of S6k

  • An important mechanism by which insulin regulates cell growth and protein synthesis is through activation of the p70 ribosomal S6 protein kinase (S6K) [5].
  • In mammalian cells, insulin-induced PI3K (phosphoinositide 3-kinase) activation, generates the lipid second messenger PtdIns(3,4,5) P (3), which is thought to play a key role in triggering the activation of S6K [5].
  • The S6k gene, located at polytene chromosome site 65D, gives rise to two predominant transcripts of 3.0 and 5.0 kb and at least two smaller transcripts (< 3.0 kb) that are found in whole-animal RNAs at all stages of development [6].
  • Conceptual translation of S6k cDNA sequences yields a product containing all of the canonical features typical of serine/threonine kinases and has 78% amino acid identity in the catalytic domain with the human p70S6k homologue [6].
  • Furthermore, all the critical phosphorylation sites required for mammalian p70s6k activation are conserved within these same domains of Dp70s6k [7].
 

Anatomical context of S6k

 

Associations of S6k with chemical compounds

  • Insulin-induced Drosophila S6 kinase activation requires phosphoinositide 3-kinase and protein kinase B [5].
  • The activity of the p70 S6K in mammalian cell is upregulated by extracellular amino acids (especially leucine) and by signals from receptor tyrosine kinases (RTKs), primarily through activation of the type 1A PI-3 kinase [9].
  • Stimulated S6 kinase activity, partially purified by Superose 6 chromatography, correlated best with the slowest migrating, approximately 65 kDa, form detected by Western analysis using a specific polyclonal antibody made to a peptide from the predicted p70S6k NH2-terminus [10].
 

Regulatory relationships of S6k

  • Here we show that, in Drosophila, dPDK1 controls cellular and organism growth by activating dAkt and S6 kinase, dS6K [11].
 

Other interactions of S6k

  • Target of Rapamycin (TOR) mediates a signalling pathway that couples amino acid availability to S6 kinase (S6K) activation, translational initiation and cell growth [12].
 

Analytical, diagnostic and therapeutic context of S6k

References

  1. Increased Rheb-TOR signaling enhances sensitivity of the whole organism to oxidative stress. Patel, P.H., Tamanoi, F. J. Cell. Sci. (2006) [Pubmed]
  2. Drosophila S6 kinase: a regulator of cell size. Montagne, J., Stewart, M.J., Stocker, H., Hafen, E., Kozma, S.C., Thomas, G. Science (1999) [Pubmed]
  3. The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila. Reiling, J.H., Hafen, E. Genes Dev. (2004) [Pubmed]
  4. Rheb is an essential regulator of S6K in controlling cell growth in Drosophila. Stocker, H., Radimerski, T., Schindelholz, B., Wittwer, F., Belawat, P., Daram, P., Breuer, S., Thomas, G., Hafen, E. Nat. Cell Biol. (2003) [Pubmed]
  5. Insulin-induced Drosophila S6 kinase activation requires phosphoinositide 3-kinase and protein kinase B. Lizcano, J.M., Alrubaie, S., Kieloch, A., Deak, M., Leevers, S.J., Alessi, D.R. Biochem. J. (2003) [Pubmed]
  6. A Drosophila gene structurally and functionally homologous to the mammalian 70-kDa s6 kinase gene. Watson, K.L., Chou, M.M., Blenis, J., Gelbart, W.M., Erikson, R.L. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  7. The Drosophila p70s6k homolog exhibits conserved regulatory elements and rapamycin sensitivity. Stewart, M.J., Berry, C.O., Zilberman, F., Thomas, G., Kozma, S.C. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  8. PAT-related amino acid transporters regulate growth via a novel mechanism that does not require bulk transport of amino acids. Goberdhan, D.C., Meredith, D., Boyd, C.A., Wilson, C. Development (2005) [Pubmed]
  9. TOR action in mammalian cells and in Caenorhabditis elegans. Long, X., Müller, F., Avruch, J. Curr. Top. Microbiol. Immunol. (2004) [Pubmed]
  10. Identification of the S6 kinase activity stimulated in quiescent brine shrimp embryos upon entry to preemergence development as p70 ribosomal protein S6 kinase: isolation of Artemia franciscana p70S6k cDNA. Santiago, J., Sturgill, T.W. Biochem. Cell Biol. (2001) [Pubmed]
  11. PDK1 regulates growth through Akt and S6K in Drosophila. Rintelen, F., Stocker, H., Thomas, G., Hafen, E. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  12. Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Gao, X., Zhang, Y., Arrazola, P., Hino, O., Kobayashi, T., Yeung, R.S., Ru, B., Pan, D. Nat. Cell Biol. (2002) [Pubmed]
 
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