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Heterogeneity of the signal transduction pathways for VEGF‐induced MAPKs activation in human vascular endothelial cells
Author(s) -
Yashima Rei,
Abe Mayumi,
Tanaka Katsuhiro,
Ueno Hikaru,
Shitara Kenya,
Takenoshita Seiichi,
Sato Yasufumi
Publication year - 2001
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1107
Subject(s) - mapk/erk pathway , p38 mitogen activated protein kinases , umbilical vein , microbiology and biotechnology , signal transduction , vascular endothelial growth factor , cancer research , biology , chemistry , vegf receptors , biochemistry , in vitro
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 Ha‐Ras 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.© 2001 Wiley‐Liss, Inc.