Linked Life Data

10400906

Source:http://linkedlifedata.com/resource/pubmed/id/10400906

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-7-30
pubmed:abstractText
PP1 has previously been described as an inhibitor of the Src-family kinases p56(Lck) and FynT. We have therefore decided to use PP1 to determine the functional role of Src in platelet-derived growth factor (PDGF)-induced proliferation and migration of human coronary artery smooth muscle cells (HCASMCs). A synthetic protocol for PP1/AGL1872 has been developed, and the inhibitory activity of PP1/AGL1872 against Src was examined. PP1/AGL1872 potently inhibited recombinant p60(c-src) in vitro and Src-dependent tyrosine phosphorylation in p60(c-srcF572)-transformed NIH3T3 cells. PP1/AGL1872 also potently inhibited PDGF-stimulated migration of HCASMCs, as determined in the modified Boyden chamber, as well as PDGF-stimulated proliferation of HCASMCs. Surprisingly, in addition to inhibition of Src kinase, PP1/AGL1872 was found to inhibit PDGF receptor kinase in cell-free assays and in various types of intact cells, including HCASMCs. PP1/AGL1872 did not inhibit phosphorylation of the vascular endothelial growth factor receptor KDR (VEGF receptor-2; kinase-insert domain containing receptor) in cell-free assays as well as in intact human coronary artery endothelial cells. In line with the insensitivity of KDR, PP1/AGL1872 had only a weak effect on vascular endothelial growth factor-stimulated migration of human coronary artery endothelial cells. On treatment of cells expressing different receptor tyrosine kinases, the activities of the epidermal growth factor receptor, fibroblast growth factor receptor-1, and insulin-like growth factor-1 receptor were resistant to PP1/AGL1872, whereas PDGF alpha-receptor was susceptible, albeit to a lesser extent than PDGF beta-receptor. These data suggest that the previously described tyrosine kinase inhibitor PP1/AGL1872 is not selective for the Src family of tyrosine kinases. It is also a potent inhibitor of the PDGF beta-receptor kinase but is not a ubiquitous tyrosine kinase inhibitor. PP1/AGL1872 inhibits migration and proliferation of HCASMCs probably by interference with 2 distinct tyrosine phosphorylation events, creating a novel and potent inhibitory principle with possible relevance for the treatment of pathological HCASMC activity, such as vascular remodeling and restenosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/4-amino-5-(4-methylphenyl)-7-(tert-b..., http://linkedlifedata.com/resource/pubmed/chemical/Endothelial Growth Factors, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Lymphokines, http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins pp60(c-src), http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles, http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Platelet-Derived Growth..., http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Platelet-Derived Growth..., http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A, http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factors, http://linkedlifedata.com/resource/pubmed/chemical/platelet-derived growth factor BB, http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12-22
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10400906-3T3 Cells, pubmed-meshheading:10400906-Animals, pubmed-meshheading:10400906-Blood Vessels, pubmed-meshheading:10400906-Cell Movement, pubmed-meshheading:10400906-Endothelial Growth Factors, pubmed-meshheading:10400906-Endothelium, Vascular, pubmed-meshheading:10400906-Enzyme Inhibitors, pubmed-meshheading:10400906-Humans, pubmed-meshheading:10400906-Lymphokines, pubmed-meshheading:10400906-Mice, pubmed-meshheading:10400906-Mitosis, pubmed-meshheading:10400906-Muscle, Smooth, Vascular, pubmed-meshheading:10400906-Platelet-Derived Growth Factor, pubmed-meshheading:10400906-Proto-Oncogene Proteins pp60(c-src), pubmed-meshheading:10400906-Pyrazoles, pubmed-meshheading:10400906-Pyrimidines, pubmed-meshheading:10400906-Receptor, Platelet-Derived Growth Factor beta, pubmed-meshheading:10400906-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:10400906-Receptors, Platelet-Derived Growth Factor, pubmed-meshheading:10400906-Vascular Endothelial Growth Factor A, pubmed-meshheading:10400906-Vascular Endothelial Growth Factors, pubmed-meshheading:10400906-src-Family Kinases
pubmed:year
1999
pubmed:articleTitle
A dual inhibitor of platelet-derived growth factor beta-receptor and Src kinase activity potently interferes with motogenic and mitogenic responses to PDGF in vascular smooth muscle cells. A novel candidate for prevention of vascular remodeling.
pubmed:affiliation
Department of Internal Medicine, Ulm University Medical Center, Ulm, Germany. johannes.waltenberger@medizin.uni-ulm.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't