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Kidney Ankyrin Repeat-containing Proteins (KANKs) comprise a family of four evolutionary conserved proteins (KANK1 to 4) that localize to the belt of mature focal adhesions (FAs) where they regulate integrin-mediated adhesion, actomyosin contractility, and link FAs to the cortical microtubule stabilization complex (CMSC). The human KANK proteins were first identified in kidney and have been associated with kidney cancer and nephrotic syndrome. Here, we report the distributions and subcellular localizations of the four Kank mRNAs and proteins in mouse tissues. We found that the KANK family members display distinct and rarely overlapping expression patterns. Whereas KANK1 is expressed at the basal side of epithelial cells of all tissues tested, KANK2 expression is mainly observed at the plasma membrane and/or cytoplasm of mesenchymal cells and KANK3 exclusively in vascular and lymphatic endothelial cells. KANK4 shows the least widespread expression pattern and when present, overlaps with KANK2 in contractile cells, such as smooth muscle cells and pericytes. Our findings show that KANKs are widely expressed in a cell type-specific manner, which suggests that they have cell- and tissue-specific functions.
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http://dx.doi.org/10.1016/j.yexcr.2020.112391 | DOI Listing |
Transl Oncol
October 2025
Department of Nephrology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China. Electronic address:
Introduction: Irreversible acute kidney injury (AKI) caused by cisplatin limits its clinical use, and transient receptor potential anchor protein 1 (TRPA1) regulates cisplatin-induced nephrotoxicity (CIN) through NF-κB signaling pathway-mediated inflammation. Single nucleotide polymorphisms in TRPA1 and NF-κB1 genes may be associated with individual heterogeneous nephrotoxicity.
Materials And Methods: In this paper, we investigated the association of 17 single nucleotide polymorphisms (SNP) of TRPA1 and NF-κB1 genes with cisplatin-induced acute nephrotoxicity.
BI 1839100 is a selective antagonist of transient receptor potential ankyrin 1 (TRPA1). Topically applied TRPA1-agonistic allyl isothiocyanate (AITC), inducing non-invasively measurable increased dermal blood flow (DBF), is known as a skin challenge model to assess TRPA1-target engagement and pharmacodynamic (PD) activity of TRPA1 inhibitors. This study aims to support the pharmacological rationale of BI 1839100 based on preclinical evidence and to test its safety, pharmacokinetic (PK) profile, and PD effects using an AITC skin challenge in a phase I first-in-human clinical study.
View Article and Find Full Text PDFMultiple cellular pathways are dysregulated in autosomal dominant polycystic kidney disease (ADPKD), but mechanisms initiating cyst formation are unknown. ADPKD is caused by mutations in genes that encode for polycystins that localize to primary cilia. The primary cilium is a miniscule subcellular compartment for generating signaling outputs that profoundly affect cellular function.
View Article and Find Full Text PDFJ Transl Med
June 2025
William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London, UK.
Background: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common genetic cause of renal failure. Uncontrolled proliferation drives ADPKD, which manifests with cystic kidney enlargement. Yet, the mechanisms by which renal epithelial cells lose cell cycle control are largely unknown.
View Article and Find Full Text PDFJ Nucl Med
July 2025
Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, Sweden; and.
Designed ankyrin repeat proteins (DARPins) are a class of engineered scaffold proteins (ESPs) with a molecular weight of approximately 15 kDa and a picomolar affinity for tumor antigen targets. Proof-of-concept studies have demonstrated the potential of DARPin radioimmunodiagnostics in humans. However, a high accumulation of activity in the kidneys limits their use in conventional radionuclide therapy.
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