Open Access

ARTICLE

PI3 kinase isoform p110δ is more important than p110α in KIT signaling in hematopoietic cells

LIANGYING ZHANG¹, SHAOTING ZHANG¹, ZHAOYANG FAN¹, ZONGYING JIANG^1,2, ANBU LIU¹, SHUJING LI^1,2, JIANMIN SUN^1,*

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

* Corresponding Authors: Jianmin Sun, ,

(This article belongs to the Special Issue: Recent Advancement in Cancer Molecular Signaling)

BIOCELL 2022, 46(9), 2081-2087. https://doi.org/10.32604/biocell.2022.020109

Received 04 November 2021; Accepted 27 January 2022; Issue published 18 May 2022

Abstract

PI3 kinases are important for KIT signaling and KIT mutants mediated cell transformation. In order to know the difference of PI3 kinase isoforms p110α and p110δ in the signaling of wild-type KIT and the often occurred KIT mutation D816V in hematopoietic malignancy mastocytosis, the predominant PI3 kinase isoform p110δ in hematopoietic tissues was knocked out in hematopoietic cells. We found that loss of p110δ expression dramatically inhibits PI3 kinase activation mediated by both wild-type KIT and KIT/D816V. By over expression of p110α in p110δ knock out cells, wild-type KIT mediated PI3 kinase activation was not changed while over expression of p110δ increased PI3 kinase activation. Similarly, in KIT/D816V expressing cells without p110δ expression, over expression of p110δ but not p110α restored PI3 kinase activation. In agreement with the signaling results, cell proliferation, cell survival and cell cycle assay further showed that over expression of p110δ but not p110α in p110δ knock out cells increases both wild-type KIT and KIT/ D816V mediated cell survival and proliferation. These results suggested that p110δ plays a more important role than p110α in KIT signaling and KIT mutant mediated cell transformation in hematopoietic cells.

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