Article (Scientific journals)
16K Human Prolactin Inhibits Vascular Endothelial Growth Factor-Induced Activation of Ras in Capillary Endothelial Cells
D'Angelo, Gisela; Martini, Jean-François; Iiri, Taroh et al.
1999In Molecular Endocrinology, 13 (2), p. 692-704
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Keywords :
16K Human Prolactin; Endothelial
Abstract :
[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
D'Angelo, Gisela;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Martini, Jean-François
Iiri, Taroh
Fantl, Wendy J.
Martial, Joseph 
Weiner, Richard I.
Language :
English
Title :
16K Human Prolactin Inhibits Vascular Endothelial Growth Factor-Induced Activation of Ras in Capillary Endothelial Cells
Publication date :
1999
Journal title :
Molecular Endocrinology
ISSN :
0888-8809
eISSN :
1944-9917
Publisher :
Endocrine Society, Chevy Chase, United States - Maryland
Volume :
13
Issue :
2
Pages :
692-704
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 04 December 2009

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