Linked Life Data

8204096

Source:http://linkedlifedata.com/resource/pubmed/id/8204096

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1994-7-6
pubmed:abstractText
Tumor-promoting phorbol esters bind to and activate protein kinase C (PKC). Staurosporine, a potent PKC inhibitor, interferes with PKC catalytic activity without altering phorbol ester binding sites in cell-free systems. We found that, unlike cell-free systems, treatment of intact platelets with staurosporine enhances the expression of phorbol 12, 13-dibutyrate (PDBu) binding sites. Incubation of platelets at 37 degrees with staurosporine (25 nM to 1 microM and 2 nM tritiated PDBu ([3H]PDBu) increased the amount of [3H]PDBu specifically bound to intact platelets by approximately 10 to 200% of control values. This effect was rapid and plateaued after 10 min of cell treatment. Scatchard analysis of the data showed that staurosporine (500 nM) significantly increased the total binding capacity Bmax from 42.9 +/- 15.4 x 10(3) to 78 +/- 7.3 x 10(3) sites per platelet and reduced the apparent dissociation constant value Kd from 30.8 +/- 8.6 nM to 9.4 +/- 3.4 nM. Enhanced PDBu binding capacity and affinity were also observed with human mononuclear and polymorphonuclear leukocytes. Fractionation of staurosporine-treated platelets showed an increased binding capacity of the particulate fraction (102%) and decreased binding capacity of the soluble fraction (60%) compared to controls, with no change in the affinity of PDBu binding to these fractions. Chelation of internal calcium with BAPTA did not significantly attenuate the staurosporine-mediated rise in PBDu binding but prevented the platelet-activating factor-induced response, indicating that cytosolic calcium does not play an important role in these staurosporine effects. These results show that, in addition to interfering with PKC protein-phosphorylating activity, staurosporine enhances PDBu binding affinity and capacity in intact platelets. This latter effect appears to be due to translocation of soluble PDBu binding sites, presumably PKC units.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1797-804
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Staurosporine up-regulates the expression of phorbol dibutyrate binding sites in human platelets.
pubmed:affiliation
Laboratoire d'Hématologie, INSERM Unité 294, Hôpital Bichat, Paris, France.
pubmed:publicationType
Journal Article