ArticleThe Journal of biological chemistry2012
Regulation of protein kinase C-related protein kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by Its N-terminal domain.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Structural basis of the protein kinase PKN1 HR1 domain oligomerization and differential regulation by RhoA and Rac1.The Journal of biological chemistry · 2026Article
- PKN2 Is a Dependency of the Mesenchymal-like Cancer Cell State.Cancer discovery · 2025Article
- Illuminating understudied kinases: a generalizable biosensor development method applied to protein kinase N.Communications biology · 2025Article
- PKN2 deficiency leads both to prenatal 'congenital' cardiomyopathy and defective angiotensin II stress responses.The Biochemical journal · 2022Article
- The structure and function of protein kinase C-related kinases (PRKs).Biochemical Society transactions · 2021Review
- Equivocal, explicit and emergent actions of PKC isoforms in cancer.Nature reviews. Cancer · 2021Review
- Phosphorylation Sites in Protein Kinases and Phosphatases Regulated by Formyl Peptide Receptor 2 Signaling.International journal of molecular sciences · 2020Review
- Development of 2-(4-pyridyl)-benzimidazoles as PKN2 chemical tools to probe cancer.Bioorganic & medicinal chemistry letters · 2020Article
- The chemical diversity and structure-based discovery of allosteric modulators for the PIF-pocket of protein kinase PDK1.Journal of enzyme inhibition and medicinal chemistry · 2019Review
- The binding affinity of PTPN13's tandem PDZ2/3 domain is allosterically modulated.BMC molecular and cell biology · 2019Article
- CagA of Helicobacter pylori interacts with and inhibits the serine-threonine kinase PRK2.Cellular microbiology · 2015Article
- Protein kinase C-related kinase 1 and 2 play an essential role in thromboxane-mediated neoplastic responses in prostate cancer.Oncotarget · 2015Article
- Conserved modular domains team up to latch-open active protein kinase Cα.The Journal of biological chemistry · 2014Article
- Protein Kinase C-Related Kinase (PKN/PRK). Potential Key-Role for PKN1 in Protection of Hypoxic Neurons.Current neuropharmacology · 2014Article
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7 authors.
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Abstract
Protein kinase C-related protein kinases (PRKs) are effectors of the Rho family of small GTPases and play a role in the development of diseases such as prostate cancer and hepatitis C. Here we examined the mechanism underlying the regulation of PRK2 by its N-terminal region. We show that the N-terminal region of PRK2 prevents the interaction with its upstream kinase, the 3-phosphoinositide-dependent kinase 1 (PDK1), which phosphorylates the activation loop of PRK2. We confirm that the N-terminal region directly inhibits the kinase activity of PRK2. However, in contrast to previous models, our data indicate that this inhibition is mediated in trans through an intermolecular PRK2-PRK2 interaction. Our results also suggest that amino acids 487-501, located in the linker region between the N-terminal domains and the catalytic domain, contribute to the PRK2-PRK2 dimer formation. This dimerization is further supported by other N-terminal domains. Additionally, we provide evidence that the region C-terminal to the catalytic domain intramolecularly activates PRK2. Finally, we discovered that the catalytic domain mediates a cross-talk between the inhibitory N-terminal region and the activating C-terminal region. The results presented here describe a novel mechanism of regulation among AGC kinases and offer new insights into potential approaches to pharmacologically regulate PRK2.
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