A5016681558- Caveolin-1 and cellular processes
- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Cancer-related Molecular Pathways
- Erythrocyte Function and Pathophysiology
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Signaling Pathways in Disease
- Cell Adhesion Molecules Research
- Cancer, Lipids, and Metabolism
- Prostate Cancer Treatment and Research
- Ion Transport and Channel Regulation
- Lipid metabolism and disorders
- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- Trypanosoma species research and implications
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- RNA modifications and cancer
- Cholesterol and Lipid Metabolism
- Cellular transport and secretion
- Ion channel regulation and function
- Cancer Mechanisms and Therapy
- Protein Kinase Regulation and GTPase Signaling
University of Salford
2016-2024
University of Manchester
2010-2018
Thomas Jefferson University
2007-2016
Sidney Kimmel Cancer Center
2007-2016
Manchester Academic Health Science Centre
2010-2016
Cancer Research UK Manchester Institute
2010-2016
Breast Cancer Now
2011-2016
Institute of Cancer Research
2012-2015
Thomas Jefferson University Hospital
2015
Breast Cancer Research Foundation
2012-2014
Here, we propose a new model for understanding the Warburg effect in tumor metabolism. Our hypothesis is that epithelial cancer cells induce (aerobic glycolysis) neighboring stromal fibroblasts. These cancer-associated fibroblasts, then undergo myo-fibroblastic differentiation, and secrete lactate pyruvate (energy metabolites resulting from aerobic glycolysis). Epithelial could take up these energy-rich use them mitochondrial TCA cycle, thereby promoting efficient energy production (ATP...
Caveolin-1 is the principal structural protein of caveolae membranes in fibroblasts and endothelia. Recently, we have shown that human CAV-1 gene localized to a suspected tumor suppressor locus, mutations Cav-1 been implicated cancer. Here, created caveolin-1 null (CAV-1 −/−) mouse model, using standard homologous recombination techniques, assess role biogenesis, endocytosis, cell proliferation, endothelial nitric-oxide synthase (eNOS) signaling. Surprisingly, mice are viable. We show these...
Caveolae are plasma membrane specializations that have been implicated in signal transduction. Caveolin, a 21-24-kDa integral protein, is principal structural component of caveolae membranes vivo. G protein α subunits concentrated purified preparations membranes, and caveolin interacts directly with multiple subunits, including Gs, Go, Gi2. Mutational or pharmacologic activation Gα prevents the interaction proteins, indicating inactive preferentially interact caveolin. Here, we show another...
GPI-linked protein molecules become Triton-insoluble during polarized sorting to the apical cell surface of epithelial cells. These insoluble complexes, enriched in cholesterol, glycolipids, and proteins, have been isolated by flotation on sucrose density gradients are thought contain putative GPI-sorting machinery. As cellular origin molecular components this complex remain unknown, we begun characterize these low-density complexes from MDCK We find that which represent 0.4-0.8% plasma...
Caveolin, a 21-24-kDa integral membrane protein, is principal component of caveolae membranes. We have suggested that caveolin functions as scaffolding protein to organize and concentrate certain caveolin-interacting proteins within In this regard, co-purifies with variety lipid-modified signaling molecules, including G-proteins, Src-like kinases, Ha-Ras, eNOS. Using several independent approaches, it has been shown 20-amino acid proximal region the cytosolic amino-terminal domain sufficient...
Caveolae are 50-100-nm membrane microdomains that represent a subcompartment of the plasma membrane. Previous morphological studies have implicated caveolae in (a) transcytosis macromolecules (including LDL and modified LDLs) across capillary endothelial cells, (b) uptake small molecules via process termed potocytosis involving GPI-linked receptor an unknown anion transport protein, (c) interactions with actin-based cytoskeleton, (d) compartmentalization certain signaling molecules,...
Endothelial nitric oxide synthase (eNOS) is a dually acylated peripheral membrane protein that targets to the Golgi region and caveolae of endothelial cells. Recent evidence has shown eNOS can co-precipitate with caveolin-1, resident coat caveolae, suggesting direct interaction between these two proteins. To test this idea, we examined interactions caveolin-1 <i>in vitro</i> vivo</i>. Incubation cell lysates or purified glutathione <i>S</i>-transferase (GST)-caveolin-1 resulted in Utilizing...
Caveolae are plasma membrane specializations present in most cell types. Caveolin, a 22-kDa integral protein, is principal structural and regulatory component of caveolae membranes. Previous studies have demonstrated that caveolin co-purifies with lipid modified signaling molecules, including Galpha subunits, H-Ras, c-Src, other related Src family tyrosine kinases. In addition, it has been shown interacts directly subunits preferentially recognizing the inactive conformation these molecules....
Caveolin, a 21-24-kDa integral membrane protein, is principal component of caveolar membranes in vivo. Caveolin interacts directly with heterotrimeric G-proteins and can functionally regulate their activity. Recently, second caveolin gene has been identified termed caveolin-2. Here, we report the molecular cloning expression third member gamily, caveolin-3. Caveolin-3 most closely related to caveolin-1 based on protein sequence homology; caveolin-3 are approximately 65% identical 85%...
Caveolae are microdomains of the plasma membrane that have been implicated in signal transduction. Caveolin, a 21–24-kDa integral protein, is principal component caveolae membrane. Recently, we and others identified family caveolin-related proteins; caveolin has retermed caveolin-1. Caveolin-3 most closely related to caveolin-1, but caveolin-3 mRNA expressed only muscle tissue types. Here, examine (i) expression protein types (ii) its localization within skeletal fibers by immunofluorescence...
Transforming growth factor-beta (TGF-beta) signaling proceeds from the cell membrane to nucleus through cooperation of type I and II serine/threonine kinase receptors their downstream SMAD effectors. Although various regulatory proteins affecting TGF-beta-mediated events have been described, relatively little is known about receptor interactions at level plasma membrane. Caveolae are cholesterol-rich microdomains that, along with marker protein caveolin-1 (Cav-1), implicated in...
Caveolae are flask-shaped plasma membrane specializations. A 22-kDa protein, caveolin, is a principal component of caveolar membranes in vivo. As recent evidence suggests that caveolae may participate G protein-coupled signaling events, we have investigated the potential interaction caveolin with heterotrimeric proteins. Using cell fractionation techniques, found mutational or pharmacologic activation Gsα prevents its cofractionation caveolin. In second independent approach, directly...
Caveolin, a 21- to 24-kDa integral membrane protein, is principal component of caveolae membranes. Caveolin interacts directly with heterotrimeric guanine nucleotide binding proteins (G proteins) and can functionally regulate their activity. Here, an approximately 20-kDa caveolin-related caveolin-2, was identified through microsequencing adipocyte-derived caveolin-enriched membranes; caveolin retermed caveolin-1. Caveolins 1 2 are similar in most respects. mRNAs for both caveolin-1...
Caveolae organelles and caveolin-1 protein expression are most abundant in adipocytes endothelial cells. Our initial report on mice lacking (Cav-1) demonstrated a loss of caveolae perturbations cell function. More recently, however, observation the Cav-1-deficient cohorts into old age revealed significantly lower body weights, as compared with wild-type controls. These results suggest that Cav-1 null may have problems lipid metabolism and/or adipocyte functioning. To test this hypothesis...