PMID- 10224060
OWN - NLM
STAT- MEDLINE
DCOM- 19990603
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 19
DP  - 1999 May 7
TI  - Akt protein kinase enhances human telomerase activity through phosphorylation of 
      telomerase reverse transcriptase subunit.
PG  - 13085-90
AB  - With the amino acid sequences of all reported Akt kinase physiological
      substrates, the possible Akt kinase substrate specificity has been suggested. The
      serine/threonine residue to be phosphorylated in these proteins is placed within 
      stretches of amino acids with homology, and the arginine residues on the -5 and
      -3 positions and a hydrophobic amino acid on the +2 position are conserved
      relative to those of serine/threonine residues (XXRXRXXS/TXX). We noticed two
      putative Akt kinase phosphorylation sites (220GARRRGGSAS229) and
      (817AVRIRGKSYV826) in human telomerase reverse transcriptase (hTERT) subunit. To 
      demonstrate that hTERT is an Akt kinase substrate protein, we performed the
      nonradioactive protein kinase assay with the fluorescein hTERT peptide
      (817AVRIRGKSYV826). We observed the phosphorylation of hTERT peptide by the human
      melanoma cell lysate or the activated recombinant Akt kinase proteins in vitro.
      With the treatment of the growth factor deprivation or okadaic acid, we also
      observed the up-regulation of both hTERT peptide phosphorylation and the
      telomerase activity. We noticed that Wortmannin down-regulates hTERT peptide
      phosphorylation and telomerase activity together. In addition, we observed the
      enhancement of telomerase activity with the pretreatment of Akt kinase in vitro. 
      Thus, these observations suggest that Akt kinase enhances human telomerase
      activity through phosphorylation of hTERT subunit as one of its substrate
      proteins.
FAU - Kang, S S
AU  - Kang SS
AD  - Shin Dong Bang R&D Center, Seoul 137-132, Republic of Korea.
FAU - Kwon, T
AU  - Kwon T
FAU - Kwon, D Y
AU  - Kwon DY
FAU - Do, S I
AU  - Do SI
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Androstadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 1W21G5Q4N2 (Okadaic Acid)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.7.49 (RNA-Directed DNA Polymerase)
RN  - EC 2.7.7.49 (Telomerase)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Amino Acid Sequence
MH  - Androstadienes/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Okadaic Acid/pharmacology
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - *Proto-Oncogene Proteins
MH  - Proto-Oncogene Proteins c-akt
MH  - RNA-Directed DNA Polymerase/*metabolism
MH  - Telomerase/chemistry/*metabolism
MH  - Tumor Cells, Cultured
MH  - Wortmannin
EDAT- 1999/05/01 00:00
MHDA- 1999/05/01 00:01
CRDT- 1999/05/01 00:00
PHST- 1999/05/01 00:00 [pubmed]
PHST- 1999/05/01 00:01 [medline]
PHST- 1999/05/01 00:00 [entrez]
AID - 10.1074/jbc.274.19.13085 [doi]
AID - S0021-9258(18)36849-2 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 May 7;274(19):13085-90. doi: 10.1074/jbc.274.19.13085.