Cited by 378PI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase SignalingMetabolism, Diabetes, and Cancer

Mitogenic Activation, Phosphorylation, and Nuclear Translocation of Protein Kinase Bβ

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Meier, Roger, Alessi, Dario R., Cron, Peter, Andjelković, Mirjana, Hemmings, Brian A.·1997·Journal of Biological Chemistry

Abstract

Protein kinase B (PKB) is a member of the second messenger-dependent family of serine/threonine kinases that has been implicated in signaling pathways downstream of growth factor receptor tyrosine kinases and phosphatidylinositol 3-kinase. Here we report the characterization of the human beta-isoform of PKB (PKBbeta). PKBbeta is ubiquitously expressed in a number of human tissues, with mRNA and protein levels elevated in heart, liver, skeletal muscle, and kidney. After transfection into HEK-293 or COS-1 cells, PKBbeta is activated 2- to 12-fold by mitogens and survival factors. Activation was due to phosphorylation on Thr-309 and Ser-474, which correspond to Thr-308 and Ser-473 implicated in the regulation of PKBalpha. Both phosphorylation and activation were prevented by the phosphatidylinositol 3-kinase inhibitor wortmannin. Moreover, membrane-targeted PKBbeta was constitutively activated when overexpressed in HEK-293 cells. Although the specific activity of PKBbeta was lower than that of PKBalpha toward Crosstide as a substrate (23 nmol/min/mg compared with 178 nmol/min/mg for PKBalpha), both enzymes showed similar substrate specificities. Using confocal microscopy, we show that activation of PKBbeta results in its nuclear translocation within 20 to 30 min after stimulation. These observations provide evidence that PKBbeta undergoes nuclear translocation upon mitogenic activation and support a role for PKB in signaling from receptor tyrosine kinases to the nucleus through phosphatidylinositol 3-kinase.

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Crossref · 10.1074/jbc.272.48.30491

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Research works printed but not linked: 3

  1. Chen, 1988, BioTechniques, 6, 632
  2. Ahmed, 1993, Oncogene, 8, 1957
  3. Andjelković, 1997, J. Biol. Chem.

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Authors
Meier, R., Alessi, D. R., Cron, P., Andjelković, M., & Hemmings, B. A.
Affiliations
  • Friedrich Miescher Institute (CH)
  • University of Dundee (GB)
Corresponding author
Hemmings, Brian A.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1997-11
Volume
272
Issue
48
Pages
30491-30497
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2112620000
Cited by
378
References
37
Citations by year
2026: 3 · 2025: 3 · 2024: 8 · 2023: 5 · 2022: 5 · 2021: 1 · 2020: 6 · 2019: 8 · 2017: 2 · 2016: 8 · 2015: 8 · 2014: 8 · 2013: 11 · 2012: 10
FWCI
7.47
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
mitogen stimulation, phosphorylation, nuclear translocation, phosphatidylinositol 3-kinase, wortmannin, receptor tyrosine kinase signaling, substrate specificity, growth factor signaling
MeSH terms
Amino Acid Sequence, Animals, Biological Transport, Cell Compartmentation, Cell Nucleus, Enzyme Activation, Growth Substances, Humans, Insulin, Insulin-Like Growth Factor I, Mitogens, Molecular Sequence Data, Phosphorylation, Phosphoserine, Phosphothreonine, Proto-Oncogene Proteins, Substrate Specificity, Tissue Distribution, Protein Serine-Threonine Kinases, COS Cells, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Rats

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