PI3 kinase isoform p110δis more important than p110αin KIT signaling in hematopoietic cells  

作　　者：LIANGYING ZHANG SHAOTING ZHANG ZHAOYANG FAN ZONGYING JIANG ANBU LIU SHUJING LI JIANMIN SUN 

机构地区：[1]NHC Key Laboratory of Metabolic Cardiovascular Diseases Research,Science and Technology Center,School of Basic Medical Sciences,Ningxia Medical University,Yinchuan,750004,China [2]General Hospital of Ningxia Medical University,Yinchuan,750004,China

出　　处：《BIOCELL》2022年第9期2081-2087,共7页生物细胞（英文）

基　　金：This work is supported by National Natural Science Foundation of China(82160521);Natural Science Foundation of Ningxia Province(2018A0089);Key Research and Development Program of Ningxia Province(2019BEH03003).

摘　　要：PI3 kinases are important for KIT signaling and KIT mutants mediated cell transformation.In order to know the difference of PI3 kinase isoforms p110αand p110δin the signaling of wild-type KIT and the often occurred KIT mutation D816V in hematopoietic malignancy mastocytosis,the predominant PI3 kinase isoform p110δin hematopoietic tissues was knocked out in hematopoietic cells.We found that loss of p110δexpression dramatically inhibits PI3 kinase activation mediated by both wild-type KIT and KIT/D816V.By over expression of p110αin p110δknock out cells,wild-type KIT mediated PI3 kinase activation was not changed while over expression of p110δincreased PI3 kinase activation.Similarly,in KIT/D816V expressing cells without p110δexpression,over expression of p110δbut not p110αrestored PI3 kinase activation.In agreement with the signaling results,cell proliferation,cell survival and cell cycle assay further showed that over expression of p110δbut not p110αin p110δknock out cells increases both wild-type KIT and KIT/D816V mediated cell survival and proliferation.These results suggested that p110δplays a more important role than p110αin KIT signaling and KIT mutant mediated cell transformation in hematopoietic cells.

关 键 词：MASTOCYTOSIS MUTATION Cell transformation 

分 类 号：R73[医药卫生—肿瘤]