Reference : 16K Human Prolactin Inhibits Vascular Endothelial Growth Factor-Induced Activation of...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
16K Human Prolactin Inhibits Vascular Endothelial Growth Factor-Induced Activation of Ras in Capillary Endothelial Cells
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 mailto [> > > >]
Weiner, Richard I. [> > > >]
Molecular Endocrinology (Baltimore, Md.)
Endocrine Society
Yes (verified by ORBi)
Chevy Chase
[en] 16K Human Prolactin ; Endothelial
[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.

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