PMID- 10490847
OWN - NLM
STAT- MEDLINE
DCOM- 19991026
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 36
DP  - 1999 Sep 9
TI  - Characterization of S6K2, a novel kinase homologous to S6K1.
PG  - 5108-14
AB  - Rapamycin is an immunosuppressant which antagonizes cellular proliferation by
      inhibiting the function of mTOR. The mTOR:FKBP12: rapamycin complex blocks G1/S
      transition by inhibiting downstream targets essential for cell cycle progression.
      One such target is p70S6k1 (S6K1), a serine/threonine kinase which is inactivated
      by the mTOR : FKBP12 : rapamycin complex, and which has been linked to
      translational control by virtue of its ability to phosphorylate the ribosomal
      protein S6. In the current work, we describe cloning and characterization of a
      novel S6K1 homolog, p54 S6 kinase 2 (p54S6k2/S6K2). Similar to S6K1, S6K2 is
      activated by mitogens and by constitutively active PI3K, and is inhibited by
      rapamycin as well as wortmannin. Differences between activation of S6K1 and S6K2 
      by PDK1 were observed, suggesting potential differences in the regulation of
      these homologs. Strikingly, S6K2 activity and S6 phosphorylation were both intact
      in S6K1-/-ES cell, indicating a possible role for S6K2 in in vivo S6
      phosphorylation. Interestingly, we found two isoforms of S6K2 which are localized
      to distinct cellular compartments; the smaller form resides in the
      detergent-soluble fraction, whereas the larger form is found in the particulate
      fraction. Our findings demonstrate the existence of a family of
      rapamycin-sensitive protein kinases potentially involved in S6 phosphorylation,
      translational control, and transduction of mTOR signals.
FAU - Lee-Fruman, K K
AU  - Lee-Fruman KK
AD  - Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, MA
      02115, USA.
FAU - Kuo, C J
AU  - Kuo CJ
FAU - Lippincott, J
AU  - Lippincott J
FAU - Terada, N
AU  - Terada N
FAU - Blenis, J
AU  - Blenis J
LA  - eng
SI  - GENBANK/AF076931
GR  - GM51405/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Isoenzymes)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Cell Line
MH  - Expressed Sequence Tags
MH  - Isoenzymes/*genetics/metabolism
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Ribosomal Protein S6 Kinases/*genetics/metabolism
MH  - *Sequence Homology, Nucleic Acid
MH  - Sirolimus/pharmacology
EDAT- 1999/09/22 00:00
MHDA- 1999/09/22 00:01
CRDT- 1999/09/22 00:00
PHST- 1999/09/22 00:00 [pubmed]
PHST- 1999/09/22 00:01 [medline]
PHST- 1999/09/22 00:00 [entrez]
AID - 10.1038/sj.onc.1202894 [doi]
PST - ppublish
SO  - Oncogene. 1999 Sep 9;18(36):5108-14. doi: 10.1038/sj.onc.1202894.