|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
1999-7-8
|
|
pubmed:abstractText |
Signaling pathways mediating the antiangiogenic action of 16K human (h)PRL include inhibition of vascular endothelial growth factor (VEGF)-induced activation of the mitogen-activated protein kinases (MAPK). To determine at which step 16K hPRL acts to inhibit VEGF-induced MAPK activation, we assessed more proximal events in the signaling cascade. 16K hPRL treatment blocked VEGF-induced Raf-1 activation as well as its translocation to the plasma membrane. 16K hPRL indirectly increased cAMP levels; however, the blockade of Raf-1 activation was not dependent on the stimulation of cAMP-dependent protein kinase (PKA), but rather on the inhibition of the GTP-bound Ras. The VEGF-induced tyrosine phosphorylation of the VEGF receptor, Flk-1, and its association with the Shc/Grb2/Ras-GAP (guanosine triphosphatase-activating protein) complex were unaffected by 16K hPRL treatment. In contrast, 16K hPRL prevented the VEGF-induced phosphorylation and dissociation of Sos from Grb2 at 5 min, consistent with inhibition by 16K hPRL of the MEK/MAPK feedback on Sos. The inhibition of Ras activation was paralleled by the increased phosphorylation of 120 kDa proteins comigrating with Ras-GAP. Taken together, these findings show that 16K hPRL inhibits the VEGF-induced Ras activation; this antagonism represents a novel and potentially important mechanism for the control of angiogenesis.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelial Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/GRB10 Adaptor Protein,
http://linkedlifedata.com/resource/pubmed/chemical/GTPase-Activating Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphokines,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Prolactin,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-raf,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vascular Endothelial...,
http://linkedlifedata.com/resource/pubmed/chemical/Son of Sevenless Proteins,
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/ras GTPase-Activating Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
0888-8809
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
13
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
692-704
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:10319320-Biological Transport,
pubmed-meshheading:10319320-Cyclic AMP,
pubmed-meshheading:10319320-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:10319320-Endothelial Growth Factors,
pubmed-meshheading:10319320-Endothelium, Vascular,
pubmed-meshheading:10319320-Enzyme Activation,
pubmed-meshheading:10319320-GRB10 Adaptor Protein,
pubmed-meshheading:10319320-GTPase-Activating Proteins,
pubmed-meshheading:10319320-Genes, ras,
pubmed-meshheading:10319320-Humans,
pubmed-meshheading:10319320-Lymphokines,
pubmed-meshheading:10319320-Membrane Proteins,
pubmed-meshheading:10319320-Peptide Fragments,
pubmed-meshheading:10319320-Prolactin,
pubmed-meshheading:10319320-Proteins,
pubmed-meshheading:10319320-Proto-Oncogene Proteins c-raf,
pubmed-meshheading:10319320-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:10319320-Receptors, Growth Factor,
pubmed-meshheading:10319320-Receptors, Vascular Endothelial Growth Factor,
pubmed-meshheading:10319320-Signal Transduction,
pubmed-meshheading:10319320-Son of Sevenless Proteins,
pubmed-meshheading:10319320-Vascular Endothelial Growth Factor A,
pubmed-meshheading:10319320-Vascular Endothelial Growth Factors,
pubmed-meshheading:10319320-ras GTPase-Activating Proteins,
pubmed-meshheading:10319320-ras Proteins
|
|
pubmed:year |
1999
|
|
pubmed:articleTitle |
16K human prolactin inhibits vascular endothelial growth factor-induced activation of Ras in capillary endothelial cells.
|
|
pubmed:affiliation |
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California School of Medicine, San Francisco 94143, USA. dangelo@ipmc.cnrs.fr
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
