TY - JOUR
T1 - K-ras/PI3K-Akt signaling is essential for zebrafish hematopoiesis and angiogenesis
AU - Liu, Lihui
AU - Zhu, Shizhen
AU - Gong, Zhiyuan
AU - Low, Boon Chuan
PY - 2008/8/6
Y1 - 2008/8/6
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0002850
DO - 10.1371/journal.pone.0002850
M3 - Article
C2 - 18682746
AN - SCOPUS:51349169062
SN - 1932-6203
VL - 3
JO - PloS one
JF - PloS one
IS - 8
M1 - e2850
ER -