ArticleMolecular and cellular biology2002
Multiple phosphoinositide 3-kinase-dependent steps in activation of protein kinase B.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 1 of them a synthesis that pooled it.
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Who cites it
137 citing papers in PubMed, 1 synthesis or guideline pooled it, 330 citations in OpenAlex.
- Pooled it
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- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Machine Learning Algorithms Identify Target Genes and the Molecular Mechanism of Matrine against Diffuse Large B-cell Lymphoma.Current computer-aided drug design · 2024Article
- Human IL-17A protein production is controlled through a PIP5K1α-dependent translational checkpoint.Science signaling · 2023Article
- The deacetylation of Akt by SIRT1 inhibits inflammation in macrophages and protects against sepsis.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- P21-Activated Kinase 4 Pak4 Maintains Embryonic Stem Cell Pluripotency via Akt Activation.Stem cells (Dayton, Ohio) · 2022Article
- The Akt Forkhead Box O Transcription Factor Axis Regulates Human Cytomegalovirus Replication.mBio · 2022Article
- Class I PI3K Biology.Current topics in microbiology and immunology · 2022Article
- Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?International journal of molecular sciences · 2021Review
- Acute Csk inhibition hinders B cell activation by constraining the PI3 kinase pathway.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Culprits or consequences: Understanding the metabolic dysregulation of muscle in diabetes.World journal of biological chemistry · 2021Review
- Long-Chain Acylcarnitines Decrease the Phosphorylation of the Insulin Receptor at Tyr1151 Through a PTP1B-Dependent Mechanism.International journal of molecular sciences · 2021Article
- Copy number aberrations drive kinase rewiring, leading to genetic vulnerabilities in cancer.Cell reports · 2021Article
- Is nuclear sirtuin SIRT6 a master regulator of immune function?American journal of physiology. Endocrinology and metabolism · 2021Review
- Regulation of mTORC2 Signaling.Genes · 2020Review
- Alterations and molecular targeting of the GSK-3 regulator, PI3K, in head and neck cancer.Biochimica et biophysica acta. Molecular cell research · 2020Review
77 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The protein kinase B (PKB)/Akt family of serine kinases is rapidly activated following agonist-induced stimulation of phosphoinositide 3-kinase (PI3K). To probe the molecular events important for the activation process, we employed two distinct models of posttranslational inducible activation and membrane recruitment. PKB induction requires phosphorylation of two critical residues, threonine 308 in the activation loop and serine 473 near the carboxyl terminus. Membrane localization of PKB was found to be a primary determinant of serine 473 phosphorylation. PI3K activity was equally important for promoting phosphorylation of serine 473, but this was separable from membrane localization. PDK1 phosphorylation of threonine 308 was primarily dependent upon prior serine 473 phosphorylation and, to a lesser extent, localization to the plasma membrane. Mutation of serine 473 to alanine or aspartic acid modulated the degree of threonine 308 phosphorylation in both models, while a point mutation in the substrate-binding region of PDK1 (L155E) rendered PDK1 incapable of phosphorylating PKB. Together, these results suggest a mechanism in which 3' phosphoinositide lipid-dependent translocation of PKB to the plasma membrane promotes serine 473 phosphorylation, which is, in turn, necessary for PDK1-mediated phosphorylation of threonine 308 and, consequentially, full PKB activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.