Aims: The 3-phosphoinositide-dependent protein kinase-1 (PDK1) activates a number of protein kinases of the AGC subfamily, including protein kinase B and ribosomal S6 protein kinase by phosphorylating these kinases at the activation-loop. PDK1 activity is regulated by auto-phosphorylation and is further increased by stimulation of cells. PDK1 has been shown to have several phosphorylation sites including 5 serine and 3 tyrosine residues. However, Ser241 and Tyr373/376 are only involved in the regulation of PDK1 activity.
Main Methods: In this study, we found the putative fragments of PDK1 by using anti-Myc and anti-PDK1 antibodies. Furthermore, the existence of four different sizes of PDK1 were confirmed with other phosphosite specific antibodies.
Key Findings: Taken together, the catalytic domain of PDK1 (42 kDa and 37 kDa) is separately existed in the cells and might be important for the regulation of subset of PDK1 substrate. Because the crystal structural studies suggested that PIF-pocket is located at the catalytic domain and plays a critical role on substrate recognition.
Significance: These suggested importance and roles of this fragment are needed to be determined. Further study on these fragments of PDK1 will provide new insight on the regulatory mechanism of PDK1 in patho-physiological condition.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.lfs.2013.09.007 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Lactoferrin conjugated radicicol nanoparticles enhanced drug delivery and cytotoxicity in prostate cancer cells.
Eur J Pharmacol
January 2025
School of Biomedical Sciences, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia; Translational Research Institute, Queensland University of Technology, Brisbane, Australia; Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia. Electronic address:
Pyruvate dehydrogenase kinase-1 (PDK1) plays a crucial role in cancer cell metabolism by regulating the glycolytic pathway. Although, inhibitors targeting PDK1 have been effective in inhibiting glycolysis in multiple cancers, their lack of selectivity leading to off-target effects limit their therapeutic benefit. Herein, we investigated the inhibitory potential of six PDK1 inhibitors on cellular proliferation, migration, and invasion of androgen-sensitive LNCaP and androgen-negative PC-3 prostate cancer cells.
View Article and Find Full Text PDFInvestigating the link between microplastic exposure (benzyl butyl phthalate) and neurodegenerative diseases using high-performance computational toxicology.
Toxicol Res (Camb)
February 2025
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Baha University, Al-Baha 65779, Saudi Arabia.
Background: Microplastics are tiny plastic particles, typically less than 5 mm in size, formed from the breakdown of larger plastic products. This breakdown releases additives, including benzyl butyl phthalate (BBP), into the environment. Humans can be exposed to BBP through contaminated food and water, inhalation, and dermal contact.
View Article and Find Full Text PDFRibosomal s6 kinase (RSK) is a mediator of aquaporin-2 S256 phosphorylation and membrane accumulation after EGFR inhibition with erlotinib.
Am J Physiol Renal Physiol
January 2025
Division of Nephrology, Program in Membrane Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Vasopressin (VP) activates protein kinase A (PKA), resulting in phosphorylation events and membrane accumulation of aquaporin-2 (AQP2). Epidermal growth factor receptor (EGFR) inhibition with erlotinib also induces AQP2 membrane trafficking with a phosphorylation pattern similar to VP, but without increasing PKA activity. Here, we identify the ribosomal s6 kinase (RSK) as a major mediator phosphorylating AQP2 in this novel, erlotinib-induced pathway.
View Article and Find Full Text PDFAn in-depth study of indolone derivatives as potential lung cancer treatment.
Sci Rep
January 2025
LIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco.
Lung cancer is a type of cancer that begins in the lungs and is one of the leading causes of cancer-related deaths worldwide. Herein an attempt to explore the relationship between the properties of indolone derivatives and their anticancer activity was investigated, implementing in silico approaches. Four indolone derivatives with the highest anticancer potential were selected to evaluate their pharmacological properties.
View Article and Find Full Text PDFSelective HDAC8 inhibition by PCI-34051 attenuates inflammation and airway remodeling in asthma miR-381-3p-TGFβ3 axis.
J Transl Int Med
December 2024
Department of Respiratory and Critical Care Medicine, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
Background And Objectives: Histone deacetylase (HDAC) families regulate various physical processes and the development of several diseases. The role of HDACs in asthma development and progression worths further investigation. This study aims to evaluate the effect of HDACs in a mouse model of asthma.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!