ArticleThrombosis and haemostasis2014
PDK1 selectively phosphorylates Thr(308) on Akt and contributes to human platelet functional responses.
Article in Thrombosis and haemostasis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- Targeting the PI3K/Akt Signaling Pathway: A Promising Therapeutic Strategy to Reduce Cancer Mortality and Overcome Chemoresistance.Health science reports · 2026Article
- Mutant p53Molecular oncology · 2026Article
- Deciphering the Medicinal Chemistry Aspects of Akt Inhibitors for the Management of Cancer: Structure-Activity Relationship Frameworks, Landscapes, and Optimization Approaches.Chemistry & biodiversity · 2026Review
- Failure of Hepatic Insulin Clearance via CEACAM1-Mediated Endocytosis: The Missing Physiological Link Between Proinsulin Misfolding, Hyperinsulinemia, and Metabolic Complications in Type 2 Diabetes, Obesity, and NAFLD.Problemy endokrinologii · 2026Review
- Establishing PDK1-based prognostic biomarkers and identifying targeted inhibitors for glioma prognosis and therapy.BMC neurology · 2026Article
- Unleashing lncRNA THOR: roles in cancer progression and clinical outlook.Molecular genetics and genomics : MGG · 2026Review
- Fractalkine (Chemokine CX3CL1) Signaling During Placentation and Placental Function.International journal of molecular sciences · 2026Review
- Phosphoinositide-dependent kinase 1 (PDK1) in cancer: molecular insights and therapeutic strategies.Frontiers in chemistry · 2026Review
- TRPA1 activation prompts lysosome-mediated Nrf2 degradation enhancing the killing of colorectal cancer cells.Redox biology · 2025Article
- Nutrient sensing receptor GPRC6A regulates mTORC1 signaling and Tau biology.Neurobiology of disease · 2025Article
- Reactive Oxygen Species: A Double-Edged Sword in the Modulation of Cancer Signaling Pathway Dynamics.Cells · 2025Review
- Differential regulation of calcium-NFAT signaling pathway by Akt isoforms: unraveling effector dynamics and exhaustion of cytotoxic T lymphocytes in tumor microenvironment.Journal for immunotherapy of cancer · 2025Article
- Emerging Targets, Novel Directions, and Innovative Approaches in Thrombosis Therapy.Aging and disease · 2025Review
- EMC2 promotes breast cancer progression and enhances sensitivity to PDK1/AKT inhibition by deubiquitinating ENO1.International journal of biological sciences · 2025Article
- Viral microRNA regulation of Akt is necessary for reactivation of Human Cytomegalovirus from latency in CD34+ hematopoietic progenitor cells and humanized mice.PLoS pathogens · 2024Article
- The Influence of Circadian Rhythms on DNA Damage Repair in Skin Photoaging.International journal of molecular sciences · 2024Review
- Tristetraprolin mediates immune evasion of mycobacterial infection in macrophages.FASEB bioAdvances · 2024Article
- The interplay between the PI3K/AKT pathway and circadian clock in physiologic and cancer-related pathologic conditions.Cell proliferation · 2024Review
- Plasma growth factors maintain constitutive translation in platelets to regulate reactivity and thrombotic potential.Blood advances · 2024Article
- A comprehensiveFrontiers in pharmacology · 2024Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
3-phosphoinositide-dependent protein kinase 1 (PDK1), a member of the protein A,G and C (AGC) family of proteins, is a Ser/Thr protein kinase that can phosphorylate and activate other protein kinases from the AGC family, including Akt at Thr308, all of which play important roles in mediating cellular responses. The functional role of PDK1 or the importance of phosphorylation of Akt on Thr308 for its activity has not been investigated in human platelets. In this study, we tested two pharmacological inhibitors of PDK1, BX795 and BX912, to assess the role of Thr308 phosphorylation on Akt. PAR4-induced phosphorylation of Akt on Thr308 was inhibited by BX795 without affecting phosphorylation of Akt on Ser473. The lack of Thr308 phosphorylation on Akt also led to the inhibition of PAR4-induced phosphorylation of two downstream substrates of Akt, viz. GSK3β and PRAS40. In vitro kinase activity of Akt was completely abolished if Thr308 on Akt was not phosphorylated. BX795 caused inhibition of 2-MeSADP-induced or collagen-induced aggregation, ATP secretion and thromboxane generation. Primary aggregation induced by 2-MeSADP was also inhibited in the presence of BX795. PDK1 inhibition also resulted in reduced clot retraction indicating its role in outside-in signalling. These results demonstrate that PDK1 selectively phosphorylates Thr308 on Akt thereby regulating its activity and plays a positive regulatory role in platelet physiological responses.
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