ArticleThe Journal of biological chemistry2016
Biphasic Regulation of Yes-associated Protein (YAP) Cellular Localization, Phosphorylation, and Activity by G Protein-coupled Receptor Agonists in Intestinal Epithelial Cells: A NOVEL ROLE FOR PROTEIN KINASE D (PKD).
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Antibody ligation of HLA class II induces YAP nuclear localization and formation of cytoplasmic YAP condensates in human endothelial cells.ImmunoHorizons · 2025Article
- Yap Is a Nutrient Sensor Sensitive to the Amino Acid L-Isoleucine and Regulates the Expression of Ctgf in Cardiomyocytes.Biomolecules · 2024Article
- Lipophilic statins inhibit YAP coactivator transcriptional activity in HCC cells through Rho-mediated modulation of actin cytoskeleton.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Lipophilic Statins Inhibit YAP Nuclear Localization, Coactivator Activity, and Migration in Response to Ligation of HLA Class I Molecules in Endothelial Cells: Role of YAP Multisite Phosphorylation.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Statins inhibit protein kinase D (PKD) activation in intestinal cells and prevent PKD1-induced growth of murine enteroids.American journal of physiology. Cell physiology · 2023Article
- TWEAK-Fn14-RelB Signaling Cascade Promotes Stem Cell-like Features that Contribute to Post-Chemotherapy Ovarian Cancer Relapse.Molecular cancer research : MCR · 2023Article
- Mechanosensitive channel Piezo1 is required for pulmonary artery smooth muscle cell proliferation.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Generation of Hydrogen Peroxide and Downstream Protein Kinase D1 Signaling Is a Common Feature of Inducers of Pancreatic Acinar-to-Ductal Metaplasia.Antioxidants (Basel, Switzerland) · 2022Article
- Article
- iTRAQ-Based Proteome Profiling of Differentially Expressed Proteins in Insulin-Resistant Human Hepatocellular Carcinoma.Frontiers in cell and developmental biology · 2022Article
- Riluzole-induced apoptosis in osteosarcoma is mediated through Yes-associated protein upon phosphorylation by c-Abl Kinase.Scientific reports · 2021Article
- Review
- MPDZ as a novel epigenetic silenced tumor suppressor inhibits growth and progression of lung cancer through the Hippo-YAP pathway.Oncogene · 2021Article
- YAP1 and its fusion proteins in cancer initiation, progression and therapeutic resistance.Developmental biology · 2021Review
- Nuclear exclusion of YAP exacerbates podocyte apoptosis and disease progression in Adriamycin-induced focal segmental glomerulosclerosis.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Ligation of HLA Class I Molecules Induces YAP Activation through Src in Human Endothelial Cells.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Concerted localization-resets precede YAP-dependent transcription.Nature communications · 2020Article
- The GEF-H1/PKD3 signaling pathway promotes the maintenance of triple-negative breast cancer stem cells.International journal of cancer · 2020Article
- Role of Hippo-YAP1/TAZ pathway and its crosstalk in cardiac biology.International journal of biological sciences · 2020Review
- YAP integrates the regulatory Snail/HNF4α circuitry controlling epithelial/hepatocyte differentiation.Cell death & disease · 2019Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
We examined the regulation of Yes-associated protein (YAP) localization, phosphorylation, and transcriptional activity in intestinal epithelial cells. Our results show that stimulation of intestinal epithelial IEC-18 cells with the G protein-coupled receptor (GPCR) agonist angiotensin II, a potent mitogen for these cells, induced rapid translocation of YAP from the nucleus to the cytoplasm (within 15 min) and a concomitant increase in YAP phosphorylation at Ser(127) and Ser(397) Angiotensin II elicited YAP phosphorylation and cytoplasmic accumulation in a dose-dependent manner (ED50 = 0.3 nm). Similar YAP responses were provoked by stimulation with vasopressin or serum. Treatment of the cells with the protein kinase D (PKD) family inhibitors CRT0066101 and kb NB 142-70 prevented the increase in YAP phosphorylation on Ser(127) and Ser(397) via Lats2, YAP cytoplasmic accumulation, and increase in the mRNA levels of YAP/TEAD-regulated genes (Ctgf and Areg). Furthermore, siRNA-mediated knockdown of PKD1, PKD2, and PKD3 markedly attenuated YAP nuclear-cytoplasmic shuttling, phosphorylation at Ser(127), and induction of Ctgf and Areg expression in response to GPCR activation. These results identify a novel role for the PKD family in the control of biphasic localization, phosphorylation, and transcriptional activity of YAP in intestinal epithelial cells. In turn, YAP and TAZ are necessary for the stimulation of the proliferative response of intestinal epithelial cells to GPCR agonists that act via PKD. The discovery of interaction between YAP and PKD pathways identifies a novel cross-talk in signal transduction and demonstrates, for the first time, that the PKDs feed into the YAP pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.