The Hippo pathway is crucial in organ size control, and its dysregulation contributes to tumorigenesis. However, upstream signals that regulate the mammalian Hippo pathway have remained elusive. Here, we report that the Hippo pathway is regulated by G-protein-coupled receptor (GPCR) signaling. Serum-borne lysophosphatidic acid (LPA) and sphingosine 1-phosphophate (S1P) act through G12/13-coupled receptors to inhibit the Hippo pathway kinases Lats1/2, thereby activating YAP and TAZ transcription coactivators, which are oncoproteins repressed by Lats1/2. YAP and TAZ are involved in LPA-induced gene expression, cell migration, and proliferation. In contrast, stimulation of Gs-coupled receptors by glucagon or epinephrine activates Lats1/2 kinase activity, thereby inhibiting YAP function. Thus, GPCR signaling can either activate or inhibit the Hippo-YAP pathway depending on the coupled G protein. Our study identifies extracellular diffusible signals that modulate the Hippo pathway and also establishes the Hippo-YAP pathway as a critical signaling branch downstream of GPCR.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433174 | PMC |
| http://dx.doi.org/10.1016/j.cell.2012.06.037 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Transcription coactivator YAP1 promotes CCND1/CDK6 expression, stimulating cell proliferation in cloned cattle placentas.
Zool Res
January 2025
State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock (R2BGL), Inner Mongolia University, Hohhot, Inner Mongolia 010070, China.
Somatic cell nuclear transfer (SCNT) has been successfully employed across various mammalian species, yet cloned animals consistently exhibit low pregnancy rates, primarily due to placental abnormalities such as hyperplasia and hypertrophy. This study investigated the involvement of the Hippo signaling pathway in aberrant placental development in SCNT-induced bovine pregnancies. SCNT-derived cattle exhibited placental hypertrophy, including enlarged abdominal circumference and altered placental cotyledon morphology.
View Article and Find Full Text PDFMechanism and therapeutic potential of hippo signaling pathway in type 2 diabetes and its complications.
Biomed Pharmacother
January 2025
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. Electronic address:
Loss of pancreatic islet cell mass and function is one of the most important factors in the development of type 2 diabetes mellitus, and hyperglycemia-induced lesions in other organs are also associated with apoptosis or hyperproliferation of the corresponding tissue cells. The Hippo signaling pathway is a key signal in the regulation of cell growth, proliferation and apoptosis, which has been shown to play an important role in the regulation of diabetes mellitus and its complications. Excessive activation of the Hippo signaling pathway under high glucose conditions triggered apoptosis and decreased insulin secretion in pancreatic islet cells, while dysregulation of the Hippo signaling pathway in the cells of other organ tissues led to proliferation or apoptosis and promoted tissue fibrosis, which aggravated the progression of diabetes mellitus and its complications.
View Article and Find Full Text PDFNoncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis.
Sci Adv
January 2025
Department of Biochemistry, College of Life Science and Biotechnology, Brain Korea 21 Project, Yonsei University, Seoul 03722, Republic of Korea.
Until now, Hippo pathway-mediated nucleocytoplasmic translocation has been considered the primary mechanism by which yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional coactivators regulate cell proliferation and differentiation via transcriptional enhanced associate domain (TEAD)-mediated target gene expression. In this study, however, we found that TAZ, but not YAP, is associated with the Golgi apparatus in macrophages activated via Toll-like receptor ligands during the resolution phase of inflammation. Golgi-associated TAZ enhanced vesicle trafficking and secretion of proinflammatory cytokines in M1 macrophage independent of the Hippo pathway.
View Article and Find Full Text PDFAltered expression profile of plasma exosomal microRNAs in exclusive electronic cigarette adult users.
Sci Rep
January 2025
Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, US.
Little is known about how exclusive e-cigarette use affects exosomal microRNA (miRNA) expression, which is crucial in inflammation and disease processes like cancer. We compared exosomal miRNA profiles between exclusive e-cigarette users and non-users. We used plasma samples from 15 exclusive e-cigarette users and 15 non-users from the Population Assessment of Tobacco and Health (PATH) Wave 1 study (2013-2014) and sequenced miRNAs with Illumina NextSeq 500/550.
View Article and Find Full Text PDFmiR-424-5p Promotes Proliferation, Migration and Invasion of Colorectal Cancer Cells via the Targeting TXNIP/Hippo Axi.
Int J Gen Med
January 2025
Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu Province, 73000, People's Republic of China.
Background: Aggressive biological behavior leads to unfavorable survival of colorectal cancer (CRC) patients. Dysregulation of TXNIP has been reported to be associated with the occurrence, proliferation and metastasis of malignancies such as liver cancer, lung cancer, kidney cancer, gastric cancer, and pancreatic cancer. MiR-424-5p has been reported as a negative regulator of TXNIP involved in lipopolysaccharide-induced acute kidney injury.
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!