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Vascular endothelial growth factor (VEGF) activates Raf‐1, mitogen‐activated protein (MAP) kinases, and S6 kinase (p90 rsk ) in cultured rat cardiac myocytes
Author(s) -
Seko Yoshinori,
Takahashi Naoyuki,
Tobe Kazuyuki,
Ueki Kohjiro,
Kadowaki Takashi,
Yazaki Yoshio
Publication year - 1998
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/(sici)1097-4652(199806)175:3<239::aid-jcp1>3.0.co;2-p
Subject(s) - myocyte , mitogen activated protein kinase , kinase , vascular endothelial growth factor , microbiology and biotechnology , protein kinase a , vascular endothelial growth factor a , cardiac myocyte , angiogenesis , biology , chemistry , medicine , cancer research , vegf receptors
Rapid activation of intracellular signaling cascades is induced in cardiac myocytes in response to various external stresses. Vascular endothelial growth factor (VEGF) is a potent angiogenic mitogen secreted from tumor cells and cells exposed to hypoxia such as ischemic myocardial cells. To clarify the mechanisms of how cardiac myocytes respond and adapt to ischemic stresses, we investigated the intracellular signaling cascades in cultured rat cardiac myocytes in response to VEGF. We show that rapid activation of mitogen‐activated protein kinase kinase kinase (MAPKKK) of Raf‐1, MAP kinases, and S6 kinase (p90 rsk ) was induced in cardiac myocytes in response to VEGF. This activation of MAP kinases was also induced in fibroblasts. VEGF also caused phosphorylation of the activating transcription factor 2. Furthermore, VEGF strongly induced a transcription factor jun ‐B mRNA in cardiac myocytes. These results indicated that MAP kinase pathway is rapidly activated in cardiac myocytes and fibroblasts in response to VEGF. It is strongly suggested that cardiac myocytes are one of the targets of VEGF and that cardiac response to ischemic stresses may be at least partly mediated by VEGF. J. Cell. Physiol. 175:239–246, 1998. © 1998 Wiley‐Liss, Inc.