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Hematology - Immunology - Molecular Biology - Physiology

Class IA PI3Kinase Regulatory Subunit, p85a, Mediates Mast Cell Development through Regulation of Growth and Survival Related Genes
Published: Wednesday, January 04, 2012
Author: Subha Krishnan et al.

by Subha Krishnan, Raghuveer Singh Mali, Karl R. Koehler, Sasidhar Vemula, Anindya Chatterjee, Joydeep Ghosh, Baskar Ramdas, Peilin Ma, Eri Hashino, Reuben Kapur

Stem cell factor (SCF) mediated KIT receptor activation plays a pivotal role in mast cell growth, maturation and survival. However, the signaling events downstream from KIT are poorly understood. Mast cells express multiple regulatory subunits of class 1A PI3Kinase (PI3K) including p85a, p85ß, p50a, and p55a. While it is known that PI3K plays an essential role in mast cells; the precise mechanism by which these regulatory subunits impact specific mast cell functions including growth, survival and cycling are not known. We show that loss of p85a impairs the growth, survival and cycling of mast cell progenitors (MCp). To delineate the molecular mechanism (s) by which p85a regulates mast cell growth, survival and cycling, we performed microarray analyses to compare the gene expression profile of MCps derived from WT and p85a-deficient mice in response to SCF stimulation. We identified 151 unique genes exhibiting altered expression in p85a-deficient cells in response to SCF stimulation compared to WT cells. Functional categorization based on DAVID bioinformatics tool and Ingenuity Pathway Analysis (IPA) software relates the altered genes due to lack of p85a to transcription, cell cycle, cell survival, cell adhesion, cell differentiation, and signal transduction. Our results suggest that p85a is involved in mast cell development through regulation of expression of growth, survival and cell cycle related genes.