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

Lihui Liu, Shizhen Zhu, Zhiyuan Gong, Boon Chuan Low

Research output: Contribution to journalArticle

36 Citations (Scopus)

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 gatal and βe3-hemoglobin, reduced blood circulation and disorganized blood vessels. Expression of either K-rasC40 that links to phosphoinositide 3-kinase (P13K) activation, or Akt2 that acts downstream of P13K, 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 P13K-specific inhibitor. Our results provide direct evidence that P13K-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.

Original languageEnglish (US)
Article numbere2850
JournalPLoS One
Volume3
Issue number8
DOIs
StatePublished - Aug 6 2008
Externally publishedYes

Fingerprint

blood circulation
hematopoiesis
1-Phosphatidylinositol 4-Kinase
Monomeric GTP-Binding Proteins
Blood Circulation
Hematopoiesis
phosphatidylinositol 3-kinase
guanosinetriphosphatase
Zebrafish
angiogenesis
Phosphatidylinositol 3-Kinases
Danio rerio
blood vessels
Knockout Mice
Embryonic Development
Blood Vessels
Vertebrates
hemoglobin
Hemoglobins
embryogenesis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

K-ras/PI3K-Akt signaling is essential for zebrafish hematopoiesis and angiogenesis. / Liu, Lihui; Zhu, Shizhen; Gong, Zhiyuan; Low, Boon Chuan.

In: PLoS One, Vol. 3, No. 8, e2850, 06.08.2008.

Research output: Contribution to journalArticle

Liu, Lihui ; Zhu, Shizhen ; Gong, Zhiyuan ; Low, Boon Chuan. / K-ras/PI3K-Akt signaling is essential for zebrafish hematopoiesis and angiogenesis. In: PLoS One. 2008 ; Vol. 3, No. 8.
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