Activation of mitogen-activated protein kinases by vascular endothelial growth factor and basic fibroblast growth factor in capillary endothelial cells is inhibited by the antiangiogenic factor 16-kDa N-terminal fragment of prolactin.
A number of factors both stimulating and inhibiting angiogenesis have been described. In the current work, we demonstrate that the angiogenic factor vascular endothelial growth factor (VEGF) activates mitogen-activated protein kinase (MAPK) as has been previously shown for basic fibroblast growth factor. The antiagiogenic factor 16-kDa N-terminal fragment of human prolactin inhibits activation of MAPK distal to autophosphorylation of the putative VEGF receptor, Flk-1, and phospholipase C-gamma. These data show that activation and inhibition of MAPK may play a central role in the control of angiogenesis.
D'Angelo
G
G
Reproductive Endocrinology Center, University of California School of Medicine, San Francisco 94143, USA.
Struman
I
I
Martial
J
J
Weiner
R I
RI
D000818:Animals; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002196:Capillaries; D002417:Cattle; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D004591:Electrophoresis, Polyacrylamide Gel; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000201:enzymology*; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology*; D008970:Molecular Weight; D010446:Peptide Fragments / Q000494:pharmacology*; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D019000:Phosphotyrosine; D011388:Prolactin / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D010446:Peptide Fragments; D010750:Phosphoproteins; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D019000:Phosphotyrosine; D014443:Tyrosine; D011388:Prolactin; D017871:Calcium-Calmodulin-Dependent Protein Kinases