Heterogeneity of the signal transduction pathways for VEGF-induced MAPKs activation in human vascular endothelial cells

Rei Yashima, Mayumi Abe, Katsuhiro Tanaka, Hikaru Ueno, Kenya Shitara, Seiichi Takenoshita, Yasufumi Sato

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) activates ERK and p38 MAPK in endothelial cells (ECs). The present study was aimed to compare its intracellular signal transduction pathways between three primary cultures of human ECs including human aortic ECs (HAECs), human umbilical vein ECs (HUVECs), and human microvascular ECs (HMVECs). VEGF activated ERK and p38 MAPK in all of three ECs. Isoforms of p38 MAPK that were activated by VEGF in HUVECs were p38-α and p38-δ. GF109203X, a specific inhibitor of PKC, markedly inhibited VEGF-induced activation of ERK and p38 MAPK in HAECs and HUVECs, whereas it exhibited little effect in HMVECs. In contrast, dominant negative mutant of HaRas almost completely abrogated VEGF-induced activation of ERK and p38 MAPK in HMVECs. Although dominant negative mutant of Ha-Ras substantially inhibited the basal activities of ERK and p38 MAPK, it exhibited marginal effect on VEGF-induced activation of ERK and p38 MAPK in HUVECs and HAECs. The activation of Ras by VEGF appeared to be most prominent in HMVECs. These results indicate that intracellular signal transduction pathways for VEGF-induced activation of MAPKs are heterogeneous and vary depending on the origin of ECs.

Original languageEnglish
Pages (from-to)201-210
Number of pages10
JournalJournal of Cellular Physiology
Volume188
Issue number2
DOIs
Publication statusPublished - 2001 Jul 19
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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