XRASGRP2 is essential for blood vessel formation during Xenopus development.
Ras guanyl nucleotide-releasing protein 2 (RASGRP2), one of the Ras guanine exchange factors, is implicated as a critical regulator of inside-out integrin activation in human lymphocytes, neutrophils and platelets. However, the activities of this protein in endothelial cells remain unclear. In the current study, we identify a physiological function in blood vessel formation for XRASGRP2, which is the Xenopus ortholog of mammalian RASGRP2. XRASGRP2 over-expression induced ectopic vascular formation, and XRASGRP2-knockdown embryos showed delayed vascular development. We also investigated the upstream signaling of XRASGRP2 in endothelium formation. XRASGRP2 expression was up-regulated in the presence of VEGF-A and down-regulated following VEGF-A depletion. XRASGRP2 knockdown abolished the ectopic induction of endothelial cells by VEGF-A in the posterior ventral blood island. These results suggest that XRASGRP2 is essential for vascular formation during Xenopus development.
Suzuki
Kan
K
Department of Pediatric Surgery and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Takahashi
Shuji
S
Haramoto
Yoshikazu
Y
Onuma
Yasuko
Y
Nagamine
Kentaro
K
Okabayashi
Koji
K
Hashizume
Kohei
K
Iwanaka
Tadashi
T
Asashima
Makoto
M
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014981:Xenopus / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*; D020663:ras Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000502:physiology*
D020662:Guanine Nucleotide Exchange Factors; C530221:Rasgrp2 protein, Xenopus; D042461:Vascular Endothelial Growth Factor A; D029867:Xenopus Proteins; D020663:ras Guanine Nucleotide Exchange Factors