Linked Life Data

10381756

Source:http://linkedlifedata.com/resource/pubmed/id/10381756

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-7-26
pubmed:abstractText
Signaling pathways of many G protein-coupled receptors overlap with those of receptor tyrosine kinases. We have found previously that alpha1-adrenergic receptors stimulate DNA synthesis and cell proliferation in human vascular smooth muscle cells; these effects were attenuated by the tyrosine protein kinase (TPK) inhibitor genistein and the mitogen-activated protein kinase (MAPK) antagonist 2-aminopurine. Experiments were designed to determine if activation of alpha1 receptors directly stimulated TPKs and MAPKs in human vascular smooth muscle cells. Norepinephrine stimulated time- and concentration-dependent tyrosine phosphorylation of multiple proteins, including p52-, 75-, 85-, 120-, and 145-kDa proteins. Increased TPK activity was demonstrated in proteins precipitated by an antiphosphotyrosine antibody, both in autophosphorylation assays and with a peptide substrate. These effects of norepinephrine were completely blocked by alpha1 receptor antagonists. A membrane-permeable Ca2+ chelator [1,2-bis(o-aminophenoxy)ethane-N,N, N',N'-tetraacetic acid tetra(acetoxymethyl)ester], completely blocked norepinephrine stimulation of phosphorylation of tyrosine proteins, suggesting that intracellular Ca2+ plays a critical role in alpha1 receptor stimulation phosphorylation of tyrosine proteins. Of the tyrosine-phosphorylated proteins, the results suggest that two of them are PLCgamma1 and adapter protein Shc. Also, alpha1 receptor stimulation caused a time-dependent increase in MAPK activity due to increased phosphorylation of p42/44(ERK1/2). The alpha1 receptor-mediated activation of MAPK was also attenuated by TPK inhibitors and intracellular Ca2+ chelator [1, 2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)ester]. These results suggest that phosphorylation of tyrosine proteins and intracellular Ca2+ plays a critical role in alpha1 receptor-stimulated MAPK signaling pathways, potentially contributing to increased DNA synthesis and cell proliferation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
290
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28-37
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:10381756-Adrenergic alpha-1 Receptor Agonists, pubmed-meshheading:10381756-Adrenergic alpha-Agonists, pubmed-meshheading:10381756-Calcium, pubmed-meshheading:10381756-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:10381756-Cell Division, pubmed-meshheading:10381756-Cells, Cultured, pubmed-meshheading:10381756-DNA, pubmed-meshheading:10381756-Enzyme Activation, pubmed-meshheading:10381756-GTP-Binding Proteins, pubmed-meshheading:10381756-Humans, pubmed-meshheading:10381756-Mitogens, pubmed-meshheading:10381756-Muscle, Smooth, Vascular, pubmed-meshheading:10381756-Norepinephrine, pubmed-meshheading:10381756-Phosphorylation, pubmed-meshheading:10381756-Phosphotyrosine, pubmed-meshheading:10381756-Precipitin Tests, pubmed-meshheading:10381756-Protein-Tyrosine Kinases
pubmed:year
1999
pubmed:articleTitle
alpha1-Adrenergic receptor stimulation of mitogenesis in human vascular smooth muscle cells: role of tyrosine protein kinases and calcium in activation of mitogen-activated protein kinase.
pubmed:affiliation
Department of Medicine, Stanford University School of Medicine, and Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA. huzhwei@leland.stanford.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't