PMID- 10490848
OWN - NLM
STAT- MEDLINE
DCOM- 19991026
LR  - 20091119
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 36
DP  - 1999 Sep 9
TI  - Cloning and characterization of a nuclear S6 kinase, S6 kinase-related kinase
      (SRK); a novel nuclear target of Akt.
PG  - 5115-9
AB  - Akt is stimulated by several growth factors, and mediates their cell survival
      signals. Recent studies have shown that Akt may play an intermediate role between
      phosphatidylinositol 3-kinase (PI3K) and p70 S6 kinase (p70S6K). Here we show
      that a novel nuclear p70S6K-related kinase (SRK) exists and that its in vivo
      function is also augmented by over-expression of Akt. Conceptual translation of
      the SRK cDNA revealed that the catalytic domain of SRK was highly homologous to
      that of p70S6K, and that the treatment of wortmannin or rapamycin strongly
      inhibited the phosphorylation and the activation of SRK, as in p70S6K. However,
      the N- and C-terminal domains of SRK were quite different from those of p70S6K.
      In immunolocalization analyses, we demonstrated a constitutive nuclear
      localization of SRK and the presence of a nuclear localization signal in its
      C-terminus. In vitro S6 phosphotransferase activities of SRK were stimulated with
      a slower kinetics by a variety of agonists to p70S6K. Interestingly,
      over-expression of the proto-oncogene Akt resulted in EGF-independent activation 
      of SRK, while over-expression of kinase-dead Akt actually had an inhibitory
      effect. This relationship between Akt and SRK suggests that SRK may be a novel
      target of Akt and perhaps an important downstream component in the nuclear
      function of Akt.
FAU - Koh, H
AU  - Koh H
AD  - Department of Biological Sciences, Korea Advanced Institute of Science and
      Technology, Kusong-dong, Yusong, Taejon 305-701, Korea.
FAU - Jee, K
AU  - Jee K
FAU - Lee, B
AU  - Lee B
FAU - Kim, J
AU  - Kim J
FAU - Kim, D
AU  - Kim D
FAU - Yun, Y H
AU  - Yun YH
FAU - Kim, J W
AU  - Kim JW
FAU - Choi, H S
AU  - Choi HS
FAU - Chung, J
AU  - Chung J
LA  - eng
SI  - GENBANK/AF099739
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (DNA, Complementary)
RN  - 0 (Retroviridae Proteins, Oncogenic)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
SB  - IM
MH  - Catalytic Domain
MH  - Cell Line
MH  - Cell Nucleus/*enzymology
MH  - Cloning, Molecular
MH  - DNA, Complementary
MH  - Humans
MH  - Molecular Sequence Data
MH  - Oncogene Protein v-akt
MH  - Retroviridae Proteins, Oncogenic/*metabolism
MH  - Ribosomal Protein S6 Kinases/*genetics/metabolism
MH  - Subcellular Fractions/enzymology
MH  - Substrate Specificity
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.1202895 [doi]
PST - ppublish
SO  - Oncogene. 1999 Sep 9;18(36):5115-9. doi: 10.1038/sj.onc.1202895.