Molecular basis for the substrate specificity of protein kinase B; comparison with MAPKAP kinase‐1 and p70 S6 kinase
Open accessAbstract
The substrate specificity of protein kinase‐Bα (PKBα, also known as RAC kinase or Akt) was investigated using synthetic peptide substrates related to the sequence surrounding the phosphorylation site on glycogen synthase kinase‐3 (GSK3). The minimum sequence motif required for efficient phosphorylation was Arg‐Xaa‐Arg‐Yaa‐Zaa‐Ser/Thr‐Hyd, where Xaa is any amino acid, Yaa and Zaa are small residues other than glycine and Hyd is a bulky hydrophobic residue (Phe, Leu). The most effective substrate, Arg‐Pro‐Arg‐Thr‐Ser‐Ser‐Phe, was phosphorylated with a K m of 5 μM and V max of 260 U/mg. PKBα phosphorylated histone H2B (K m 5 μM, V max 68 Ulmg) specifically at Ser‐36 which also lies in an Arg‐Xaa‐Arg‐Xaa‐Xaa‐Ser‐Hyd motif. The peptide Arg‐Pro‐Arg‐Ala‐Ala‐Thr‐Phe may be a relatively specific substrate for PKBα because, unlike other substrates, it is not phosphorylated by p70 S6 kinase or MAP kinase activated protein (MAPKAP) kinase‐1.
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The region surrounding Ser166 and Ser188 in human Mdm2 conforms to a consensus sequence motif for PKB phosphorylation, RXRXX(S/T).
“The region surrounding Ser 166 and Ser 188 in human Mdm2 conforms to a consensus sequence motif for PKB phosphorylation, i.e.RXRXX(S/T) (36).”
From Stabilization of Mdm2 via Decreased Ubiquitination Is Mediated by Protein Kinase B/Akt-dependent Phosphorylation (2004) · cites this paper as [36]
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- Authors
- Alessi, D. R., Barry Caudwell, F., Andjelkovic, M., Hemmings, B. A., & Cohen, P.
- Affiliations
- University of Dundee (GB)
- Friedrich Miescher Institute (CH)
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 1996-12-16
- Volume
- 399
- Issue
- 3
- Pages
- 333-338
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2165863663
- Cited by
- 628
- References
- 21
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 7 · 2023: 10 · 2022: 10 · 2021: 17 · 2020: 11 · 2019: 13 · 2018: 10 · 2017: 16 · 2016: 12 · 2015: 19 · 2014: 23 · 2013: 17 · 2012: 18
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion, other-oa)
- Funders
- Royal Society
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- Akt, substrate specificity, phosphorylation motifs, glycogen synthase kinase-3, histone H2B, p70 S6 kinase, synthetic peptide substrates
- MeSH terms
- Amino Acid Sequence, Histones, Humans, Infant, Newborn, Molecular Sequence Data, Phosphorylation, Proto-Oncogene Proteins, Substrate Specificity, Protein Serine-Threonine Kinases, Ribosomal Protein S6 Kinases, Ribosomal Protein S6 Kinases, 90-kDa, Proto-Oncogene Proteins c-akt
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