|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
11
|
|
pubmed:dateCreated |
2003-5-15
|
|
pubmed:abstractText |
Receptor tyrosine kinases (RTKs) direct diverse cellular and developmental responses by stimulating a relatively small number of overlapping signaling pathways. Specificity may be determined by RTK expression patterns or by differential activation of individual signaling pathways. To address this issue we generated knock-in mice in which the extracellular domain of the mouse platelet-derived growth factor alpha receptor (PDGFalphaR) is fused to the cytosolic domain of Drosophila Torso (alpha(Tor)) or the mouse fibroblast growth factor receptor 1 (alpha(FR)). alpha(Tor) homozygous embryos exhibit significant rescue of neural crest and angiogenesis defects normally found in PDGFalphaR-null embryos yet fail to rescue skeletal or extraembryonic defects. This phenotype was associated with the ability of alpha(Tor) to stimulate the mitogen-activated protein (MAP) kinase pathway to near wild-type levels but failure to completely activate other pathways, such as phosphatidylinositol (PI) 3-kinase. The alpha(FR) chimeric receptor fails to rescue any aspect of the PDGFalphaR-null phenotype. Instead, alpha(FR) expression leads to a gain-of-function phenotype highlighted by ectopic bone development. The alpha(FR) phenotype was associated with a failure to limit MAP kinase signaling and to engage significant PI3-kinase response. These results suggest that precise regulation of divergent downstream signaling pathways is critical for specification of RTK function.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-10380925,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-10419690,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-10500190,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-10647936,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-11051543,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-11124809,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-11239463,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-11259511,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-11290305,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-11447289,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-11585811,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-11714681,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-11782318,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-1322269,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-1322271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-1326293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-1334404,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-1375321,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-1379698,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-1653172,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-1668277,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-1846043,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-2561060,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-7834738,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-8193540,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-8330523,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-8598287,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-9154000,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-9182757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-9226440,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-9545195,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-9632781,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-9660748,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-9710453,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12748302-9885560
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD31,
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fgfr1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Fibroblast Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Platelet-Derived Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Fibroblast Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/torso protein, Drosophila
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jun
|
|
pubmed:issn |
0270-7306
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
23
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
4013-25
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:12748302-Animals,
pubmed-meshheading:12748302-Antigens, CD31,
pubmed-meshheading:12748302-Blood Vessels,
pubmed-meshheading:12748302-Bone and Bones,
pubmed-meshheading:12748302-Cell Line,
pubmed-meshheading:12748302-Drosophila Proteins,
pubmed-meshheading:12748302-Drosophila melanogaster,
pubmed-meshheading:12748302-Embryo, Mammalian,
pubmed-meshheading:12748302-Embryo, Nonmammalian,
pubmed-meshheading:12748302-Evolution, Molecular,
pubmed-meshheading:12748302-Fibroblasts,
pubmed-meshheading:12748302-Genes, Reporter,
pubmed-meshheading:12748302-Mice,
pubmed-meshheading:12748302-Mice, Transgenic,
pubmed-meshheading:12748302-Neural Crest,
pubmed-meshheading:12748302-Phenotype,
pubmed-meshheading:12748302-Placenta,
pubmed-meshheading:12748302-Receptor, Fibroblast Growth Factor, Type 1,
pubmed-meshheading:12748302-Receptor, Platelet-Derived Growth Factor alpha,
pubmed-meshheading:12748302-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:12748302-Receptors, Fibroblast Growth Factor,
pubmed-meshheading:12748302-Recombinant Fusion Proteins,
pubmed-meshheading:12748302-Signal Transduction
|
|
pubmed:year |
2003
|
|
pubmed:articleTitle |
Evolutionary divergence of platelet-derived growth factor alpha receptor signaling mechanisms.
|
|
pubmed:affiliation |
Program in Developmental Biology and Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|
