Akt Protein Kinase Enhances Human Telomerase Activity through Phosphorylation of Telomerase Reverse Transcriptase Subunit

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...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-05, Vol.274 (19), p.13085-13090
Main Authors: Kang, Sang Sun, Kwon, Taegun, Kwon, Do Yoon, Do, Su Il
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Androstadienes - pharmacology
Enzyme Inhibitors - pharmacology
Humans
Okadaic Acid - pharmacology
Phosphorylation
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Protein-Serine-Threonine Kinases - metabolism
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-akt
RNA-Directed DNA Polymerase - metabolism
Telomerase - chemistry
Telomerase - metabolism
Tumor Cells, Cultured
Wortmannin
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.274.19.13085