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dc.contributor.authorDavis, Roger J.
dc.contributor.authorGirones, Nuria
dc.contributor.authorFaucher, Mark
dc.date2022-08-11T08:10:05.000
dc.date.accessioned2022-08-23T16:54:41Z
dc.date.available2022-08-23T16:54:41Z
dc.date.issued1988-04-15
dc.date.submitted2008-08-15
dc.identifier.citationJ Biol Chem. 1988 Apr 15;263(11):5373-9.
dc.identifier.issn0021-9258 (Print)
dc.identifier.pmid3258597
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42557
dc.description.abstractEpidermal growth factor (EGF) and transforming growth factor alpha bind to a common receptor at the cell surface. Both the affinity and the tyrosine protein kinase activity of the receptor are regulated by exogenous factors, such as platelet-derived growth factor. A protein kinase C-dependent (Ca2+/phospholipid-dependent enzyme) and independent regulatory mechanism have been described. The protein kinase C-dependent mechanism results in the inhibition of the affinity and tyrosine kinase activity of the EGF receptor. We describe in this report an alternative mechanism of regulation of the receptor that is mediated by sphingosine. Treatment of WI-38 human fetal lung fibroblasts with 5 microM sphingosine for 2 min at 37 degrees C caused a marked increase in the affinity of the EGF receptor. Similar results were obtained when isolated plasma membranes prepared from these cells were incubated with sphingosine. A stimulation of the EGF receptor tyrosine protein kinase activity was also observed after sphingosine-treatment of plasma membranes. Sphingosine caused a decrease in the Km for ATP and an increase in the Vmax for the tyrosine phosphorylation of a synthetic peptide substrate. Control experiments demonstrated that these actions of sphingosine were not secondary to the inhibition of protein kinase C. These data indicate that sphingosine causes the functional conversion of the EGF receptor into an activated state that expresses both a high affinity for EGF and an increased tyrosine kinase activity. We conclude that sphingosine is a bioactive molecule in human fibroblasts.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=3258597&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://www.jbc.org/content/263/11/5373.full.pdf+html
dc.subjectAnimals
dc.subjectCells, Cultured
dc.subjectChromatography, High Pressure Liquid
dc.subjectEpidermal Growth Factor
dc.subjectKinetics
dc.subjectPeptides
dc.subjectPhosphorylation
dc.subjectProtein-Tyrosine Kinases
dc.subjectReceptor, Epidermal Growth Factor
dc.subjectSphingosine
dc.subjectTemperature
dc.subjectTransforming Growth Factors
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleTwo alternative mechanisms control the interconversion of functional states of the epidermal growth factor receptor
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume263
dc.source.issue11
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/895
dc.identifier.contextkey579784
html.description.abstract<p>Epidermal growth factor (EGF) and transforming growth factor alpha bind to a common receptor at the cell surface. Both the affinity and the tyrosine protein kinase activity of the receptor are regulated by exogenous factors, such as platelet-derived growth factor. A protein kinase C-dependent (Ca2+/phospholipid-dependent enzyme) and independent regulatory mechanism have been described. The protein kinase C-dependent mechanism results in the inhibition of the affinity and tyrosine kinase activity of the EGF receptor. We describe in this report an alternative mechanism of regulation of the receptor that is mediated by sphingosine. Treatment of WI-38 human fetal lung fibroblasts with 5 microM sphingosine for 2 min at 37 degrees C caused a marked increase in the affinity of the EGF receptor. Similar results were obtained when isolated plasma membranes prepared from these cells were incubated with sphingosine. A stimulation of the EGF receptor tyrosine protein kinase activity was also observed after sphingosine-treatment of plasma membranes. Sphingosine caused a decrease in the Km for ATP and an increase in the Vmax for the tyrosine phosphorylation of a synthetic peptide substrate. Control experiments demonstrated that these actions of sphingosine were not secondary to the inhibition of protein kinase C. These data indicate that sphingosine causes the functional conversion of the EGF receptor into an activated state that expresses both a high affinity for EGF and an increased tyrosine kinase activity. We conclude that sphingosine is a bioactive molecule in human fibroblasts.</p>
dc.identifier.submissionpathoapubs/895
dc.contributor.departmentDepartment of Biochemistry
dc.source.pages5373-9


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