Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2006-2-20
pubmed:abstractText
Caveolae are flask-shaped endocytic structures composed primarily of caveolin-1 (Cav1) and caveolin-2 (Cav2) proteins. Interestingly, a cytoplasmic accumulation of Cav1 protein does not always result in a large number of assembled caveolae organelles, suggesting a regulatory mechanism that controls caveolae assembly. In this study we report that stimulation of epithelial cells with epithelial growth factor (EGF) results in a profound increase in the number of caveolar structures at the plasma membrane. Human pancreatic tumor cells (PANC-1) and normal rat kidney cells (NRK), as a control, were treated with 30 ng/ml EGF for 0, 5, and 20 min before fixation and viewing by electron microscopy. Cells fixed without EGF treatment exhibited modest numbers of plasma membrane-associated caveolae. Cells treated with EGF for 5 or 20 min showed an 8-10-fold increase in caveolar structures, some forming long, pronounced caveolar "towers" at the cell-cell borders. It is known that Cav1 is Src-phosphorylated on tyrosine 14 in response to EGF treatment, although the significance of this modification is unknown. We postulated that phosphorylation could provide the stimulus for caveolae assembly. To this end, we transfected cells with mutant forms of Cav1 that could not be phosphorylated (Cav1Y14F) and tested if this altered protein reduced the number of EGF-induced caveolae. We observed that EGF-stimulated PANC-1 cells expressing the mutant Cav1Y14F protein exhibited a 90-95% reduction in caveolae number compared with cells expressing wild type Cav1. This study provides novel insights into how cells regulate caveolae formation and implicates EGF-based signaling cascades in the phosphorylation of Cav1 as a stimulus for caveolae assembly.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4570-9
pubmed:meshHeading
pubmed-meshheading:16332692-Animals, pubmed-meshheading:16332692-Blotting, Western, pubmed-meshheading:16332692-Caveolin 1, pubmed-meshheading:16332692-Cell Line, pubmed-meshheading:16332692-Cell Line, Tumor, pubmed-meshheading:16332692-Cell Membrane, pubmed-meshheading:16332692-Centrifugation, Density Gradient, pubmed-meshheading:16332692-Cytoplasm, pubmed-meshheading:16332692-Dogs, pubmed-meshheading:16332692-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:16332692-Enzyme Inhibitors, pubmed-meshheading:16332692-Epidermal Growth Factor, pubmed-meshheading:16332692-Epithelial Cells, pubmed-meshheading:16332692-Humans, pubmed-meshheading:16332692-Immunoprecipitation, pubmed-meshheading:16332692-Microscopy, Electron, Transmission, pubmed-meshheading:16332692-Microscopy, Fluorescence, pubmed-meshheading:16332692-Microscopy, Immunoelectron, pubmed-meshheading:16332692-Mutation, pubmed-meshheading:16332692-Phosphorylation, pubmed-meshheading:16332692-Rats, pubmed-meshheading:16332692-Sucrose, pubmed-meshheading:16332692-Time Factors, pubmed-meshheading:16332692-Transfection, pubmed-meshheading:16332692-Tyrosine
pubmed:year
2006
pubmed:articleTitle
Epithelial growth factor-induced phosphorylation of caveolin 1 at tyrosine 14 stimulates caveolae formation in epithelial cells.
pubmed:affiliation
Center for Basic Research in Digestive Diseases and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905, USA.
pubmed:publicationType
Journal Article