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PLoS One. 2008 Aug 6;3(8):e2850. doi: 10.1371/journal.pone.0002850.

K-ras/PI3K-Akt signaling is essential for zebrafish hematopoiesis and angiogenesis.

Author information

1
Department of Biological Sciences, Cell Signaling and Developmental Biology Laboratory, The National University of Singapore, Singapore, The Republic of Singapore.

Abstract

The RAS small GTPases orchestrate multiple cellular processes. Studies on knock-out mice showed the essential and sufficient role of K-RAS, but not N-RAS and H-RAS in embryonic development. However, many physiological functions of K-RAS in vivo remain unclear. Using wild-type and fli1:GFP transgenic zebrafish, we showed that K-ras-knockdown resulted in specific hematopoietic and angiogenic defects, including the impaired expression of erythroid-specific gene gata1 and sse3-hemoglobin, reduced blood circulation and disorganized blood vessels. Expression of either K-rasC40 that links to phosphoinositide 3-kinase (PI3K) activation, or Akt2 that acts downstream of PI3K, could rescue both hematopoietic and angiogenic defects in the K-ras knockdown. Consistently, the functional rescue by k-ras mRNA was significantly suppressed by wortmannin, a PI3K-specific inhibitor. Our results provide direct evidence that PI3K-Akt plays a crucial role in mediating K-ras signaling during hematopoiesis and angiogenesis in vivo, thus offering new targets and alternative vertebrate model for studying these processes and their related diseases.

PMID:
18682746
PMCID:
PMC2483249
DOI:
10.1371/journal.pone.0002850
[Indexed for MEDLINE]
Free PMC Article

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