AI Article Synopsis
Article Abstract
CRK and CRKL encode cytoplasmic adaptors that contribute to the etiology of congenital heart disease. Neural crest cells (NCCs) are required for cardiac outflow tract (OFT) septation and aortic arch formation. The roles of Crk/Crkl in NCCs during mouse cardiovascular development remain unknown. To test this, we inactivated Crk and/or Crkl in NCCs. We found that the loss of Crk, rather than Crkl, in NCCs resulted in double outlet right ventricle, while loss of both Crk/Crkl in NCCs resulted in severe defects with earlier lethality due to failed OFT septation and severe dilation of the pharyngeal arch arteries (PAAs). We found that these defects are due to altered cell morphology resulting in reduced localization of NCCs to the OFT and failed integrity of the PAAs, along with reduced expression of Integrin signaling genes. Further, molecular studies identified reduced differentiation of vascular smooth muscle cells that may in part be due to altered Notch signaling. Additionally, there is increased cellular stress that leads to modest increase in apoptosis. Overall, this explains the mechanism for the Crk/Crkl phenotype.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029238 | PMC |
| http://dx.doi.org/10.1093/hmg/ddab313 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Abl kinases regulate FGF signaling independent of Crk phosphorylation to prevent Peters anomaly.
bioRxiv
October 2024
Departments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Article Synopsis
- Peters anomaly, a leading cause of congenital corneal opacity, is linked to corneal-lenticular adhesion and is tied to unidentified mutations and a complex disease mechanism.
- Abl kinases have been discovered as key regulators of FGF signaling, with their genetic deletion allowing lens formation even when FGF is missing, and their role appears independent of traditional ERK signaling pathways.
- The study suggests that targeting the Ptpn12-p130Cas pathway, which is influenced by Abl kinases, could offer therapeutic possibilities for addressing Peters anomaly by improving lens vesicle separation dynamics.
SLAMF7 (CD319) on activated CD8 T cells transduces environmental cues to initiate cytotoxic effector cell responses.
Cell Death Differ
October 2024
Department of Experimental Paediatrics, University Hospital, Otto-von-Guericke-University, Magdeburg, Germany.
CD8 T-cell responses are meticulously orchestrated processes regulated by intercellular receptor:ligand interactions. These interactions critically control the dynamics of CD8 T-cell populations that is crucial to overcome threats such as viral infections or cancer. Yet, the mechanisms governing these dynamics remain incompletely elucidated.
View Article and Find Full Text PDFBlockade of Crk eliminates Yki/YAP-activated tumors via JNK-mediated apoptosis in Drosophila.
Commun Biol
September 2024
Laboratory of Genetics, Graduate School of Biostudies, Kyoto University, 46-29, Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Selective elimination of cancer cells without causing deleterious effects on normal cells is an ideal anti-cancer strategy. Here, using Drosophila cancer model, we performed an in vivo RNAi screen for anti-cancer targets that selectively eliminate tumors without affecting normal tissue growth. In Drosophila imaginal epithelium, clones of cells expressing oncogenic Ras with simultaneous mutations in the cell polarity gene scribble (Ras/scrib) develop into malignant tumors.
View Article and Find Full Text PDFCRKL Enhances YAP Signaling through Binding and JNK/JUN Pathway Activation in Liver Cancer.
Int J Mol Sci
August 2024
Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
The Hippo pathway transducers yes-associated protein (YAP) and WW-domain containing transcription regulator 1 (WWTR1/TAZ) are key regulators of liver tumorigenesis, promoting tumor formation and progression. Although the first inhibitors are in clinical trials, targeting the relevant upstream regulators of YAP/TAZ activity could prove equally beneficial. To identify regulators of YAP/TAZ activity in hepatocarcinoma (HCC) cells, we carried out a proximity labelling approach (BioID) coupled with mass spectrometry.
View Article and Find Full Text PDFCrk mediates Csk-Hippo signaling independently of Yap tyrosine phosphorylation to induce cell extrusion.
bioRxiv
July 2024
Department of Ophthalmology, Columbia University, New York, NY 10032, USA.
Src family kinases (SFKs), including Src, Fyn and Yes, play important roles in development and cancer. Despite being first discovered as the Yes-associated protein, the regulation of Yap by SFKs remains poorly understood. Here, through single-cell analysis and genetic lineage tracing, we show that the pan-epithelial ablation of C-terminal Src kinase (Csk) in the lacrimal gland unleashes broad Src signaling but specifically causes extrusion and apoptosis of acinar progenitors at a time when they are shielded by myoepithelial cells from the basement membrane.
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!