PMID- 15341740
OWN - NLM
STAT- MEDLINE
DCOM- 20050124
LR  - 20170225
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 14
IP  - 17
DP  - 2004 Sep 7
TI  - SKAR is a specific target of S6 kinase 1 in cell growth control.
PG  - 1540-9
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) and phosphatidylinositol 
      3-kinase (PI3K) signaling pathways promote cell growth and cell cycle progression 
      in response to nutritional, energy, and mitogenic cues. In mammalian cells, the 
      ribosomal protein S6 kinases, S6K1 and S6K2, lie downstream of mTOR and PI3K, 
      suggesting that translational control through the phosphorylation of S6 regulates 
      cell growth. Interestingly, genetic experiments predict that a substrate that is 
      specific to S6K1 but not S6K2 regulates cell growth. RESULTS: Here we identify 
      SKAR as a novel and specific binding partner and substrate of S6K1 but not S6K2. 
      We find that serines 383 and 385 of human SKAR are insulin-stimulated and 
      rapamycin-sensitive S6K1 phosphorylation sites. Quantitative mass spectrometry 
      reveals that serine 383/385 phosphorylation is sensitive to RNA interference 
      (RNAi)-mediated S6K1 reduction, but not S6K2 reduction. Furthermore, 
      RNAi-mediated reduction of SKAR decreases cell size. SKAR is nuclear protein with 
      homology to the Aly/REF family of RNA binding proteins, which has been proposed 
      to couple transcription with pre-mRNA splicing and mRNA export. CONCLUSIONS: We 
      have identified a novel and specific target of S6K1, SKAR, which regulates cell 
      growth. The homology of SKAR to the Aly/REF family links S6K1 with mRNA 
      biogenesis in the control of cell growth.
FAU - Richardson, Celeste J
AU  - Richardson CJ
AD  - Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
FAU - Broenstrup, Mark
AU  - Broenstrup M
FAU - Fingar, Diane C
AU  - Fingar DC
FAU - Julich, Kristina
AU  - Julich K
FAU - Ballif, Bryan A
AU  - Ballif BA
FAU - Gygi, Steven
AU  - Gygi S
FAU - Blenis, John
AU  - Blenis J
LA  - eng
SI  - RefSeq/NP_115687
SI  - RefSeq/NP_573321
SI  - RefSeq/NP_835237
SI  - RefSeq/XP_203662
SI  - RefSeq/XP_235521
GR  - F32CA69808/CA/NCI NIH HHS/United States
GR  - GM51405/GM/NIGMS NIH HHS/United States
GR  - T32CA09361/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Nuclear Proteins)
RN  - 0 (POLDIP3 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Cell Division/physiology
MH  - Cell Size
MH  - Fluorescent Antibody Technique, Indirect
MH  - *Gene Expression Regulation
MH  - Glutathione Transferase
MH  - Humans
MH  - Immunoprecipitation
MH  - Mass Spectrometry
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/metabolism
MH  - Peptide Mapping
MH  - Phosphorylation
MH  - Protein Binding
MH  - RNA Interference
MH  - RNA, Messenger/*metabolism
MH  - RNA-Binding Proteins/*genetics/*metabolism
MH  - Ribosomal Protein S6 Kinases/*metabolism
MH  - Sequence Analysis, DNA
MH  - *Signal Transduction
MH  - Two-Hybrid System Techniques
EDAT- 2004/09/03 05:00
MHDA- 2005/01/26 09:00
CRDT- 2004/09/03 05:00
PHST- 2004/04/11 00:00 [received]
PHST- 2004/06/09 00:00 [revised]
PHST- 2004/07/19 00:00 [accepted]
PHST- 2004/09/03 05:00 [pubmed]
PHST- 2005/01/26 09:00 [medline]
PHST- 2004/09/03 05:00 [entrez]
AID - S0960-9822(04)00653-0 [pii]
AID - 10.1016/j.cub.2004.08.061 [doi]
PST - ppublish
SO  - Curr Biol. 2004 Sep 7;14(17):1540-9. doi: 10.1016/j.cub.2004.08.061.