Linked Life Data

17227773

Source:http://linkedlifedata.com/resource/pubmed/id/17227773

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2007-3-12
pubmed:abstractText
Membrane-permeable calmodulin inhibitors, such as the napthalenesulfonamide derivatives W-7/W-13, trifluoperazine, and calmidazolium, are used widely to investigate the role of calcium/calmodulin (Ca2+/CaM) in living cells. If two chemically different inhibitors (e.g. W-7 and trifluoperazine) produce similar effects, investigators often assume the effects are due to CaM inhibition. Zeta potential measurements, however, show that these amphipathic weak bases bind to phospholipid vesicles at the same concentrations as they inhibit Ca2+/CaM; this suggests that they also bind to the inner leaflet of the plasma membrane, reducing its negative electrostatic surface potential. This change will cause electrostatically bound clusters of basic residues on peripheral (e.g. Src and K-Ras4B) and integral (e.g. epidermal growth factor receptor (EGFR)) proteins to translocate from the membrane to the cytoplasm. We measured inhibitor-mediated translocation of a simple basic peptide corresponding to the calmodulin-binding juxtamembrane region of the EGFR on model membranes; W-7/W-13 causes translocation of this peptide from membrane to solution, suggesting that caution must be exercised when interpreting the results obtained with these inhibitors in living cells. We present evidence that they exert dual effects on autophosphorylation of EGFR; W-13 inhibits epidermal growth factor-dependent EGFR autophosphorylation under different experimental conditions, but in the absence of epidermal growth factor, W-13 stimulates autophosphorylation of the receptor in four different cell types. Our interpretation is that the former effect is due to W-13 inhibition of Ca2+/CaM, but the latter results could be due to binding of W-13 to the plasma membrane.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8474-86
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17227773-Animals, pubmed-meshheading:17227773-Calmodulin, pubmed-meshheading:17227773-Cell Membrane, pubmed-meshheading:17227773-Dose-Response Relationship, Drug, pubmed-meshheading:17227773-Enzyme Inhibitors, pubmed-meshheading:17227773-Humans, pubmed-meshheading:17227773-Membrane Potentials, pubmed-meshheading:17227773-Mice, pubmed-meshheading:17227773-Models, Biological, pubmed-meshheading:17227773-Models, Chemical, pubmed-meshheading:17227773-Phospholipids, pubmed-meshheading:17227773-Phosphorylation, pubmed-meshheading:17227773-Protein Binding, pubmed-meshheading:17227773-Receptor, Epidermal Growth Factor, pubmed-meshheading:17227773-Static Electricity, pubmed-meshheading:17227773-Sulfonamides, pubmed-meshheading:17227773-Surface Properties, pubmed-meshheading:17227773-Time Factors
pubmed:year
2007
pubmed:articleTitle
Membrane-permeable calmodulin inhibitors (e.g. W-7/W-13) bind to membranes, changing the electrostatic surface potential: dual effect of W-13 on epidermal growth factor receptor activation.
pubmed:affiliation
Department of Physiology and Biophysics, Health Science Center, State University of New York at Stony Brook, Stony Brook, New York 11794-8661, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural