The Two PDGF Receptors Maintain Conserved Signaling In Vivo despite Divergent Embryological Functions
Gene targeting studies have indicated that the two receptors for PDGF, α and β, direct unique functions during development. Distinct ligand affinities, patterns of gene expression, and/or mechanisms of signal relay may account for functional specificity of the two PDGF receptor isoforms. To distingu...
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| Veröffentlicht in: | Molecular cell 2001-02, Vol.7 (2), p.343-354 |
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| creator | Klinghoffer, Richard A Mueting-Nelsen, Peter F Faerman, Alexander Shani, Moshe Soriano, Philippe |
| description | Gene targeting studies have indicated that the two receptors for PDGF, α and β, direct unique functions during development. Distinct ligand affinities, patterns of gene expression, and/or mechanisms of signal relay may account for functional specificity of the two PDGF receptor isoforms. To distinguish between these factors, we have created two complementary lines of knockin mice in which the intracellular signaling domains of one PDGFR have been removed and replaced by those of the other PDGFR. While both lines demonstrated substantial rescue of normal development, substitution of the PDGFβR signaling domains with those of the PDGFαR resulted in varying degrees of vascular disease. This observation provides a framework for discussing the evolution of receptor tyrosine kinase functional specificity. |
| doi_str_mv | 10.1016/S1097-2765(01)00182-4 |
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Mueting-Nelsen, Peter F ; Faerman, Alexander ; Shani, Moshe ; Soriano, Philippe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-4e06e2e9186b51449950a0000b7da02647c2ee95fb32f8bd390608ca5fc527283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Cells, Cultured</topic><topic>Gene Deletion</topic><topic>Gene Targeting - methods</topic><topic>Genetic Complementation Test</topic><topic>Genotype</topic><topic>Glomerulonephritis - genetics</topic><topic>Glomerulonephritis - pathology</topic><topic>Heart Defects, Congenital - genetics</topic><topic>Heart Defects, Congenital - pathology</topic><topic>Histocytochemistry</topic><topic>Kidney - abnormalities</topic><topic>Kidney - embryology</topic><topic>Kidney - pathology</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Phosphorylation</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Protein Structure, Tertiary</topic><topic>Receptor, Platelet-Derived Growth Factor alpha - genetics</topic><topic>Receptor, Platelet-Derived Growth Factor alpha - metabolism</topic><topic>Receptor, Platelet-Derived Growth Factor beta - genetics</topic><topic>Receptor, Platelet-Derived Growth Factor beta - metabolism</topic><topic>receptor-tyrosine kinase</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Retina - abnormalities</topic><topic>Retina - embryology</topic><topic>Retina - pathology</topic><topic>Signal Transduction</topic><topic>Thrombosis - genetics</topic><topic>Thrombosis - pathology</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Klinghoffer, Richard A</creatorcontrib><creatorcontrib>Mueting-Nelsen, Peter F</creatorcontrib><creatorcontrib>Faerman, Alexander</creatorcontrib><creatorcontrib>Shani, Moshe</creatorcontrib><creatorcontrib>Soriano, Philippe</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Klinghoffer, Richard A</au><au>Mueting-Nelsen, Peter F</au><au>Faerman, Alexander</au><au>Shani, Moshe</au><au>Soriano, Philippe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Two PDGF Receptors Maintain Conserved Signaling In Vivo despite Divergent Embryological Functions</atitle><jtitle>Molecular cell</jtitle><addtitle>Mol Cell</addtitle><date>2001-02-01</date><risdate>2001</risdate><volume>7</volume><issue>2</issue><spage>343</spage><epage>354</epage><pages>343-354</pages><issn>1097-2765</issn><eissn>1097-4164</eissn><abstract>Gene targeting studies have indicated that the two receptors for PDGF, α and β, direct unique functions during development. Distinct ligand affinities, patterns of gene expression, and/or mechanisms of signal relay may account for functional specificity of the two PDGF receptor isoforms. To distinguish between these factors, we have created two complementary lines of knockin mice in which the intracellular signaling domains of one PDGFR have been removed and replaced by those of the other PDGFR. While both lines demonstrated substantial rescue of normal development, substitution of the PDGFβR signaling domains with those of the PDGFαR resulted in varying degrees of vascular disease. This observation provides a framework for discussing the evolution of receptor tyrosine kinase functional specificity.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11239463</pmid><doi>10.1016/S1097-2765(01)00182-4</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Cells, Cultured Gene Deletion Gene Targeting - methods Genetic Complementation Test Genotype Glomerulonephritis - genetics Glomerulonephritis - pathology Heart Defects, Congenital - genetics Heart Defects, Congenital - pathology Histocytochemistry Kidney - abnormalities Kidney - embryology Kidney - pathology Mice Mice, Transgenic Mitogen-Activated Protein Kinases - metabolism Phosphorylation Protein Isoforms - genetics Protein Isoforms - metabolism Protein Structure, Tertiary Receptor, Platelet-Derived Growth Factor alpha - genetics Receptor, Platelet-Derived Growth Factor alpha - metabolism Receptor, Platelet-Derived Growth Factor beta - genetics Receptor, Platelet-Derived Growth Factor beta - metabolism receptor-tyrosine kinase Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Retina - abnormalities Retina - embryology Retina - pathology Signal Transduction Thrombosis - genetics Thrombosis - pathology Time Factors |
| title | The Two PDGF Receptors Maintain Conserved Signaling In Vivo despite Divergent Embryological Functions |
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