Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-9-21
pubmed:abstractText
Angiotensin (Ang) II has 2 major receptor isoforms, Ang type 1 (AT(1)) and Ang type (AT(2)). AT(1) transphosphorylates epidermal growth factor receptor (EGFR) to activate extracellular signal-regulated kinase (ERK). Although AT(2) was shown to inactivate ERK, the action of AT(2) on EGFR activation remains undefined. Using AT(2)-overexpressing vascular smooth muscle cells from AT(2) transgenic mice, we studied these undefined actions of AT(2). Maximal ERK activity induced by Ang II was increased 1.9- and 2.2-fold by AT(2) inhibition, which was abolished by orthovanadate but not okadaic acid or pertussis toxin. AT(2) inhibited AT(1)-mediated EGFR tyrosine phosphorylation by 63%. The activity of SHP-1 tyrosine phosphatase was significantly upregulated 1 minute after AT(2) stimulation and association of SHP-1 with EGFR was increased, whereas AT(2) failed to tyrosine phosphorylate SHP-1. Stable overexpression of SHP-1-dominant negative mutant completely abolished AT(2)-mediated inhibition of EGFR and ERK activation. AT(1)-mediated c-fos mRNA accumulation was attenuated by 48% by AT(2) stimulation. Induction of fibronectin gene containing an AP-1 responsive element in its 5'-flanking region was decreased by 37% after AT(2) stimulation, corresponding to the results of gel mobility assay with the AP-1 sequence of fibronectin as a probe. These findings suggested that AT(2) inhibits ERK activity by inducing SHP-1 activity, leading to decreases in AP-1 activity and AP-1-regulated gene expression, in which EGFR dephosphorylation plays an important role via association of SHP-1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II, http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins, http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/PD 123319, http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine, http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase..., http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase..., http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase..., http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos, http://linkedlifedata.com/resource/pubmed/chemical/Ptpn11 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Ptpn6 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Pyridines, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Angiotensin, Type 1, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Angiotensin, Type 2, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Angiotensin, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
367-72
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11566906-Angiotensin II, pubmed-meshheading:11566906-Animals, pubmed-meshheading:11566906-Cells, Cultured, pubmed-meshheading:11566906-Fibronectins, pubmed-meshheading:11566906-Gene Expression Regulation, pubmed-meshheading:11566906-Imidazoles, pubmed-meshheading:11566906-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:11566906-Mice, pubmed-meshheading:11566906-Mice, Transgenic, pubmed-meshheading:11566906-Mitogen-Activated Protein Kinases, pubmed-meshheading:11566906-Muscle, Smooth, Vascular, pubmed-meshheading:11566906-Phosphorylation, pubmed-meshheading:11566906-Phosphotyrosine, pubmed-meshheading:11566906-Protein Binding, pubmed-meshheading:11566906-Protein Tyrosine Phosphatase, Non-Receptor Type 1, pubmed-meshheading:11566906-Protein Tyrosine Phosphatase, Non-Receptor Type 11, pubmed-meshheading:11566906-Protein Tyrosine Phosphatase, Non-Receptor Type 6, pubmed-meshheading:11566906-Protein Tyrosine Phosphatases, pubmed-meshheading:11566906-Proto-Oncogene Proteins c-fos, pubmed-meshheading:11566906-Pyridines, pubmed-meshheading:11566906-RNA, Messenger, pubmed-meshheading:11566906-Receptor, Angiotensin, Type 1, pubmed-meshheading:11566906-Receptor, Angiotensin, Type 2, pubmed-meshheading:11566906-Receptor, Epidermal Growth Factor, pubmed-meshheading:11566906-Receptors, Angiotensin, pubmed-meshheading:11566906-Transcription Factor AP-1
pubmed:year
2001
pubmed:articleTitle
Angiotensin II type 2 receptor inhibits epidermal growth factor receptor transactivation by increasing association of SHP-1 tyrosine phosphatase.
pubmed:affiliation
Department of Medicine II, Kansai Medical University, Moriguchi, Osaka, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't