|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
13
|
|
pubmed:dateCreated |
1999-4-29
|
|
pubmed:abstractText |
The epidermal growth factor receptor (EGFR) mediates the actions of a family of bioactive peptides that include epidermal growth factor (EGF) and amphiregulin (AR). Here we have studied AR and EGF mitogenic signaling in EGFR-devoid NR6 fibroblasts that ectopically express either wild type EGFR (WT) or a truncated EGFR that lacks the three major sites of autophosphorylation (c'1000). COOH-terminal truncation of the EGFR significantly impairs the ability of AR to (i) stimulate DNA synthesis, (ii) elicit Elk-1 transactivation, and (iii) generate sustained enzymatic activation of mitogen-activated protein kinase. EGFR truncation had no significant effect on AR binding to receptor but did result in defective GRB2 adaptor function. In contrast, EGFR truncation did not impair EGF mitogenic signaling, and in c'1000 cells EGF was able to stimulate the association of ErbB2 with GRB2 and SHC. Elk-1 transactivation was monitored when either ErbB2 or a truncated dominant-negative ErbB2 mutant (ErbB2-(1-813)) was overexpressed in cells. Overexpression of full-length ErbB2 resulted in a strong constitutive transactivation of Elk-1 in c'1000 but only slightly stimulated Elk-1 in WT or parental NR6 cells. Conversely, overexpression of ErbB2-(1-813) inhibited EGF-stimulated Elk-1 transactivation in c'1000 but not in WT cells. Thus, the cytoplasmic tail of the EGFR plays a critical role in AR mitogenic signaling but is dispensable for EGF, since EGF-activated truncated EGFRs can signal through ErbB2.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ELK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 Adaptor Protein,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogens,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/amphiregulin,
http://linkedlifedata.com/resource/pubmed/chemical/ets-Domain Protein Elk-1
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Mar
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
26
|
|
pubmed:volume |
274
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
8900-9
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:10085134-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:10085134-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:10085134-Cell Line,
pubmed-meshheading:10085134-DNA Replication,
pubmed-meshheading:10085134-DNA-Binding Proteins,
pubmed-meshheading:10085134-Enzyme Activation,
pubmed-meshheading:10085134-GRB2 Adaptor Protein,
pubmed-meshheading:10085134-Genes, Reporter,
pubmed-meshheading:10085134-Glycoproteins,
pubmed-meshheading:10085134-Growth Substances,
pubmed-meshheading:10085134-Humans,
pubmed-meshheading:10085134-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:10085134-Kinetics,
pubmed-meshheading:10085134-Mitogens,
pubmed-meshheading:10085134-Mutation,
pubmed-meshheading:10085134-Phosphorylation,
pubmed-meshheading:10085134-Phosphotyrosine,
pubmed-meshheading:10085134-Protein Binding,
pubmed-meshheading:10085134-Proteins,
pubmed-meshheading:10085134-Proto-Oncogene Proteins,
pubmed-meshheading:10085134-Receptor, Epidermal Growth Factor,
pubmed-meshheading:10085134-Receptor, erbB-2,
pubmed-meshheading:10085134-Recombinant Fusion Proteins,
pubmed-meshheading:10085134-Signal Transduction,
pubmed-meshheading:10085134-Transcription Factors,
pubmed-meshheading:10085134-Transcriptional Activation,
pubmed-meshheading:10085134-ets-Domain Protein Elk-1
|
|
pubmed:year |
1999
|
|
pubmed:articleTitle |
A differential requirement for the COOH-terminal region of the epidermal growth factor (EGF) receptor in amphiregulin and EGF mitogenic signaling.
|
|
pubmed:affiliation |
Division of Cytokine Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|
