CASK

Last update 08 May 2025

Basic Info

Synonyms

CAGH39, calcium/calmodulin dependent serine protein kinase, Calcium/calmodulin-dependent serine protein kinase

+ [9]

Introduction

Multidomain scaffolding Mg(2+)-independent protein kinase that catalyzes the phosphotransfer from ATP to proteins such as NRXN1, and plays a role in synaptic transmembrane protein anchoring and ion channel trafficking (PubMed:18423203). Contributes to neural development and regulation of gene expression via interaction with the transcription factor TBR1. Binds to cell-surface proteins, including amyloid precursor protein, neurexins and syndecans. May mediate a link between the extracellular matrix and the actin cytoskeleton via its interaction with syndecan and with the actin/spectrin-binding protein 4.1. Component of the LIN-10-LIN-2-LIN-7 complex, which associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (By similarity).

100 Clinical Results associated with CASK

100 Translational Medicine associated with CASK

0 Patents (Medical) associated with CASK

687

Literatures (Medical) associated with CASK

01 Mar 2025·Molecular Genetics & Genomic Medicine

Approaches to Evaluate Whole Exome Sequencing Data That Incorporate Genetic Intolerance Scores for Congenital Anomalies, Including Intronic Regions Adjacent to Exons

Article

Author: Ogata‐Kawata, Hiroko ; Nakabayashi, Kazuhiko ; Ito, Yushi ; Hata, Kenichiro ; Taniguchi, Kosuke ; Ozawa, Katsusuke ; Wada, Seiji ; Fukui, Kana ; Okamura, Kohji ; Hasegawa, Fuyuki ; Migita, Ohsuke ; Kawai, Tomoko ; Aoto, Saki ; Sago, Haruhiko ; Hori, Asuka ; Okazaki, Yuka

ABSTRACTBackgroundWhole exome sequencing (WES) aids in diagnosing monogenic diseases, yet > 50% of all cases remain undiagnosed. We aimed to improve diagnostic precision by developing an effective WES‐based strategy for detecting congenital anomalies.MethodsInitially, 128 probands with congenital anomalies were assessed using trio‐WES and copy number variation analysis—variant interpretation was for exons and splice sites. Thereafter, we reanalyzed the sequence data for undiagnosed cases using the following methods. First, we performed trio‐WES analysis, adding genetic intolerance scores annotation. Second, we analyzed all exons, splicing sites, and intron variants for cases with phenotypes suggestive of specific causative genes using SpliceAI. Lastly, using SpliceAI, we analyzed all exons, splicing sites, and intron variants in genetically constrained genes filtered with genetic intolerance scores.ResultsInitial analysis diagnosed 51 of 128 cases (39.8%). In the reanalysis, first, we identified novel likely pathogenic variants in MED12 and CCDC22 associated with X‐linked diseases. Second, a novel TMEM67 intron variant associated with Meckel syndrome was detected. Finally, a de novo hemizygous pathogenic intronic variant in CASK was identified in a case of intrauterine fetal death.ConclusionsWES analysis, including intronic regions and utilizing genetic intolerance scores, has the potential to efficiently improve diagnostic yield.

01 Feb 2025·Neuropharmacology

Neuroprotection by 4R-cembranoid against Gulf War Illness-related Chemicals is mediated by ERK, PI3K, and CaMKII pathways

Article

Author: Marrero Valentín, José L ; Tosado-Rodríguez, Eduardo L ; Ferchmin, Pedro A ; Roche Lima, Abiel ; Sabeva, Nadezhda ; Ferchmin, Pedro A. ; Rivera-Moctezuma, Félix G. ; Vázquez Alicia, Sorangely ; Tosado-Rodríguez, Eduardo L. ; Pérez, Dinely ; Marrero Valentín, José L. ; Alicia, Sorangely Vázquez ; Rivera-Moctezuma, Félix G

Gulf War Illness (GWI) has been consistently linked to exposure to pyridostigmine (PB), N,N-Diethyl-meta-toluamide (DEET), permethrin (PER), and traces of sarin. In this study, diisopropylfluorophosphate (DFP, sarin surrogate) and the GWI-related chemicals were found to reduce the number of functionally active neurons in rat hippocampal slices. These findings confirm a link between GWI neurotoxicants and N-Methyl-D-Aspartate (NMDA)-mediated excitotoxicity, which was successfully reversed by Edelfosine (a phospholipase Cβ (PLCβ3) inhibitor) and Flupirtine (a Kv7 channel agonist). To test whether 4R-cembranoid (4R), a nicotinic α7 acetylcholinesterase receptor (α7AChR) modulator known for its neuroprotective properties, can restore hippocampal neurons from glutamate-induced neurotoxicity, we exposed rat hippocampal slices with DFP for 10 min followed by 60 min treatment with 4R. We investigated the 4R mechanisms of neuroprotection after preincubation with LY294002, PD98059, and KN-62. The inhibition of the phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MEK1/2), and calcium/calmodulin-dependent protein kinase (CaMKII) abrogated the protective effect of 4R against DFP-induced neurotoxicity. In separate experiments, after incubation with DFP, followed by 4R for 1 h, cellular extracts were prepared for Western blotting of phospho-Akt, phospho-GSK3β, phosphorylated extracellular signal-regulated kinase (ERK)1/2, CaMKII and cAMP response element-binding protein (CREB). Our results show that DFP induces neuronal dysfunction by dephosphorylation, while 4R restores the phosphorylation of Akt, GSK3, ERK1/2, CREB, and CaMKII. Moreover, our proteomics analysis supported the notion that 4R activates additional signaling pathways related to enhancing neuronal signaling, synaptic plasticity, and apoptotic inhibition to promote cell survival against DFP, offering biomarkers for developing treatment against GWI.

01 Jan 2025·International Immunopharmacology

Isoferulic acid regulates CXCL12/CXCR4-mediated apoptosis and autophagy in podocyte and mice with STZ-induced diabetic nephropathy

Article

Author: Ni, Boran ; Chang, Aqian ; Qu, Changhai ; Hu, Panxiang ; Yao, Aina ; Dong, Xiaoxv ; Peng, Hulinyue ; Yin, Xingbin ; Liu, Jing ; Ni, Jian ; Huang, Huating

Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus and a major cause of end-stage renal disease. Isoferulic acid (IFA) is a phenolic compound that has strong antioxidant, anti-inflammatory, and hypoglycemic effects. Researches and our previous study showed the potential anti-diabetic capacity and anti- oxidative stress damage targeting podocytes of IFA. The purpose of this study was to investigate whether IFA protects MPC5 podocytes from high glucose damage and alleviates DN symptoms in STZ-induced mice, as well as to explore the mechanism. The findings revealed that IFA (10, 25, 50 μM) significantly reduced high glucose-mediated toxicity, abnormal motility and morphology, ROS release, Ca²⁺ elevation with MPTP opening, apoptotic alterations with Caspase-3/7 activity increase and CXCL12 chemotaxis and interaction with CXCR4 in MPC5 podocytes. Furthermore, IFA increased Podocalyxin and LC3 II/I ratio. Meanwhile, IFA suppressed p53, mTOR, CASK, and p62. Furthermore, IFA has the ability to directly influence downstream mTOR, p53, and CASK apoptotic and podocyte motility regulatory targets when inhibiting the CXCL12/CXCR4 signaling pathway. In the sequent in vivo experiment, the results showed STZ-induced DN mice had higher kidney index, urination, UACR, lipid metabolism abnormalities and renal dysfunction, raised blood glucose, and podocyte damage than normal C57BL/6 mice. However, IFA treatment (50 mg/kg, 25 mg/kg, and 12.5 mg/kg) for 10 weeks restored the DN symptoms in the mice. IFA treatment elevated LC3B and LC3 II/I ratios and decreased p62 via suppressing chemokine axis CXCL12/CXCR4 with PI3K/Akt/mTOR, MMP9, and NF-κB p65 and activating podocyte markers WT1, nephrin, and Podocalyxin, thereby inducing autophagy and mitigating apoptosis in the DN mice kidneys. These findings suggest that IFA protective mechanism on kidney and podocytes simulating DN symptoms is primarily mediated by the CXCL12/CXCR4 pathways with the inactivation of apoptotic pathways and activation of autophagy.

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