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

Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6374-8. doi: 10.1073/pnas.92.14.6374.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Capillaries
  • Cattle
  • Cells, Cultured
  • Cerebrovascular Circulation
  • Electrophoresis, Polyacrylamide Gel
  • Endothelial Growth Factors / pharmacology*
  • Endothelium, Vascular / enzymology*
  • Enzyme Activation
  • Fibroblast Growth Factor 2 / pharmacology*
  • Humans
  • Lymphokines / pharmacology*
  • Molecular Weight
  • Peptide Fragments / pharmacology*
  • Phosphoproteins / isolation & purification
  • Phosphoproteins / metabolism
  • Phosphotyrosine
  • Prolactin / pharmacology*
  • Recombinant Proteins / pharmacology
  • Tyrosine / analogs & derivatives
  • Tyrosine / analysis
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Lymphokines
  • Peptide Fragments
  • Phosphoproteins
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Fibroblast Growth Factor 2
  • Phosphotyrosine
  • Tyrosine
  • Prolactin
  • Calcium-Calmodulin-Dependent Protein Kinases