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Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is an activating kinase for calcium/calmodulin-dependent protein kinase type 1 (CaMKI), calcium/calmodulin-dependent protein kinase type IV (CaMKIV), RAC-alpha serine/threonine-protein kinase (PKB), and AMP-activated protein kinase (AMPK) that has been reported to form an active oligomer in cells. Glutathione S-transferase (GST) pulldown assay from the extracts of COS-7 cells expressing GST- and His-CaMKKα/1 mutants showed that the C-terminal region containing the autoinhibitory and calmodulin (CaM)-binding sequence (residues 438-463) is required for CaMKKα/1 homo-oligomerization. This was confirmed by the fact that the GST-CaMKKα/1 C-terminal domain (residues 435-505) directly interacted with EGFP-CaMKKα/1 residues 435-505 as well as with wild-type CaMKKα/1. Notably, once oligomerized in cells, CaMKKα/1 is neither exchangeable between the oligomeric complexes nor dissociated by Ca/CaM binding. These results support stable oligomerization of CaMKK in the cells by intermolecular self-association of its C-terminal region containing a regulatory domain.
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http://dx.doi.org/10.1002/1873-3468.70078 | DOI Listing |
Lab Anim Res
September 2025
Department of Pathology, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
Background: Stroke-prone spontaneously hypertensive rats (SHRSP) exhibit slow-twitch muscle-specific hypotrophy compared with normotensive Wistar-Kyoto rats (WKY). Because slow-twitch muscles are prone to disuse atrophy, SHRSP may experience both disuse atrophy and impaired recovery from it. This study investigated the response of SHRSP to disuse atrophy and subsequent recovery, using WKY as a control.
View Article and Find Full Text PDFCell Mol Immunol
September 2025
Pediatric Intensive Care Unit, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences); Department of Immunology, School of Basic Medical Sciences; Department of Clinical Laboratory, the Third Affiliated Hospital of Southern Medical University, Southern Medical University, Gua
Communication between group 3 innate lymphoid cells (ILC3) and other immune cells, as well as intestinal epithelial cells, is pivotal in regulating intestinal inflammation. This study, for the first time, underscores the importance of crosstalk between intestinal endothelial cells (ECs) and ILC3. Our single-cell transcriptome analysis combined with protein expression detection revealed that ECs significantly increased the population of interleukin (IL)-22 ILC3 through interactions mediated by endothelin-1 (ET-1) and its receptor endothelin A receptor (EDNRA).
View Article and Find Full Text PDFUrol Oncol
September 2025
Nutritional, Genes and Human Disease Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh. Electronic address:
Background: Understanding the mutational landscape is critical for elucidating the molecular mechanisms driving cancer progression. This study aimed to profile somatic mutations in bladder cancer patients (N=7) from Bangladesh to provide insights into the genetic alterations underlying this malignancy.
Methods: We performed targeted sequencing of 50 oncogenes and tumor suppressor genes using the Ion AmpliSeq Cancer Hotspot Panel v2 on tumor and matched blood samples from seven bladder cancer patients.
Nucleic Acids Res
September 2025
Department of Microbiology, Institute of Biology, University of Kassel, 34132 Kassel, Germany.
Casein kinase 1 (CK1) family members are crucial for ER-Golgi trafficking, calcium signalling, DNA repair, transfer RNA (tRNA) modifications, and circadian rhythmicity. Whether and how substrate interactions and kinase autophosphorylation contribute to CK1 plasticity remains largely unknown. Here, we undertake a comprehensive phylogenetic, cellular, and molecular characterization of budding yeast CK1 Hrr25 and identify human CK1 epsilon (CK1ϵ) as its ortholog.
View Article and Find Full Text PDFBioorg Med Chem Lett
September 2025
Galapagos SASU, 102 avenue Gaston Roussel, 93230 Romainville, France. Electronic address:
The salt-inducible kinase (SIK) family encompasses three isoforms, SIK1, SIK2, and SIK3, which are members of the AMP-activated protein kinase (AMPK) family of serine/threonine protein kinases. SIK inhibition has emerged as a potential therapeutic approach across multiple indications, as SIKs regulate a diverse set of physiological processes such as metabolism, bone remodeling, immune response, malignancies, skin pigmentation, and circadian rhythm. Within isoform-specific SIK inhibitors there is a need to understand the distinct role of each protein, and here we describe the first SIK1 selective inhibitors.
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