Linked Life Data

8662819

Source:http://linkedlifedata.com/resource/pubmed/id/8662819

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
1996-8-15
pubmed:abstractText
The epidermal growth factor receptor (EGFR) is regulated by at least two mechanisms involving protein kinase C (PKC), inhibition of EGF binding and inhibition of EGF-stimulated tyrosine kinase activity. In this study we investigated whether mitogen-activated protein kinase (MAPK) mediates the inhibitory effects of PKC on EGFR binding or kinase activity by pretreating NIH3T3 and Chinese hamster ovary cells expressing the EGFR with PD98059, an inhibitor of MAPK/extracellular signal-regulated kinase kinase (MEK). We also determined whether substitution of cysteine for threonine at residue 669, the site of MAPK phosphorylation of the EGFR, alters the inhibition of kinase activity by PKC. The results indicate that 1) PKC down-regulates EGFR tyrosine kinase activity by an MEK-dependent mechanism presumably involving MAPK; 2) the inhibition by PKC is not a direct result of phosphorylation of the EGFR by PKC or MAPK; 3) activation of MAPK is not sufficient to regulate EGFR kinase activity; and 4) PKC-mediated down-regulation of EGF binding and EGFR kinase activity occur by different mechanisms. These data are consistent with a model for regulation of the EGFR by other receptors whereby their activation of PKC, in conjunction with MAPK, results in the phosphorylation of a protein(s) that modulates EGFR kinase activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12891-6
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:8662819-3T3 Cells, pubmed-meshheading:8662819-Animals, pubmed-meshheading:8662819-CHO Cells, pubmed-meshheading:8662819-Cricetinae, pubmed-meshheading:8662819-Cysteine, pubmed-meshheading:8662819-Down-Regulation, pubmed-meshheading:8662819-Enzyme Activation, pubmed-meshheading:8662819-Epidermal Growth Factor, pubmed-meshheading:8662819-Mice, pubmed-meshheading:8662819-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:8662819-Mutagenesis, Site-Directed, pubmed-meshheading:8662819-Phorbol 12,13-Dibutyrate, pubmed-meshheading:8662819-Phosphorylation, pubmed-meshheading:8662819-Protein Binding, pubmed-meshheading:8662819-Protein Kinase C, pubmed-meshheading:8662819-Protein Kinase Inhibitors, pubmed-meshheading:8662819-Protein Kinases, pubmed-meshheading:8662819-Receptor, Epidermal Growth Factor, pubmed-meshheading:8662819-Signal Transduction, pubmed-meshheading:8662819-Terpenes, pubmed-meshheading:8662819-Thapsigargin, pubmed-meshheading:8662819-Tyrosine
pubmed:year
1996
pubmed:articleTitle
Role of mitogen-activated protein kinase kinase in regulation of the epidermal growth factor receptor by protein kinase C.
pubmed:affiliation
Ben May Institute and Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, Illinois 60637, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't