Unknown

Dataset Information

0

Ras signaling directs endothelial specification of VEGFR2+ vascular progenitor cells.


ABSTRACT: Vascular endothelial growth factor receptor 2 (VEGFR2) transmits signals of crucial importance to vasculogenesis, including proliferation, migration, and differentiation of vascular progenitor cells. Embryonic stem cell-derived VEGFR2(+) mesodermal cells differentiate into mural lineage in the presence of platelet derived growth factor (PDGF)-BB or serum but into endothelial lineage in response to VEGF-A. We found that inhibition of H-Ras function by a farnesyltransferase inhibitor or a knockdown technique results in selective suppression of VEGF-A-induced endothelial specification. Experiments with ex vivo whole-embryo culture as well as analysis of H-ras(-/-) mice also supported this conclusion. Furthermore, expression of a constitutively active H-Ras[G12V] in VEGFR2(+) progenitor cells resulted in endothelial differentiation through the extracellular signal-related kinase (Erk) pathway. Both VEGF-A and PDGF-BB activated Ras in VEGFR2(+) progenitor cells 5 min after treatment. However, VEGF-A, but not PDGF-BB, activated Ras 6-9 h after treatment, preceding the induction of endothelial markers. VEGF-A thus activates temporally distinct Ras-Erk signaling to direct endothelial specification of VEGFR2(+) vascular progenitor cells.

SUBMITTER: Kawasaki K 

PROVIDER: S-EPMC2287293 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

Ras signaling directs endothelial specification of VEGFR2+ vascular progenitor cells.

Kawasaki Kyoko K   Watabe Tetsuro T   Sase Hitoshi H   Hirashima Masanori M   Koide Hiroshi H   Morishita Yasuyuki Y   Yuki Keiko K   Sasaoka Toshikuni T   Suda Toshio T   Katsuki Motoya M   Miyazono Kohei K   Miyazawa Keiji K  

The Journal of cell biology 20080401 1


Vascular endothelial growth factor receptor 2 (VEGFR2) transmits signals of crucial importance to vasculogenesis, including proliferation, migration, and differentiation of vascular progenitor cells. Embryonic stem cell-derived VEGFR2(+) mesodermal cells differentiate into mural lineage in the presence of platelet derived growth factor (PDGF)-BB or serum but into endothelial lineage in response to VEGF-A. We found that inhibition of H-Ras function by a farnesyltransferase inhibitor or a knockdow  ...[more]

Similar Datasets

| S-EPMC3243534 | biostudies-literature
| S-EPMC10575733 | biostudies-literature
| S-EPMC3841787 | biostudies-literature
| 2028928 | ecrin-mdr-crc
| S-EPMC5143324 | biostudies-other
| S-EPMC6553980 | biostudies-literature
| S-EPMC2862130 | biostudies-literature
| S-EPMC8415364 | biostudies-literature
| S-EPMC6885617 | biostudies-literature
| S-EPMC3974272 | biostudies-literature