title: Class I(A) PI3Kinase regulatory subunit, p85α, mediates mast cell development through regulation of growth and survival related genes.
abstract: 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 1(A) PI3Kinase (PI3K) including p85α, p85β, p50α, and p55α. 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 p85α impairs the growth, survival and cycling of mast cell progenitors (MCp). To delineate the molecular mechanism (s) by which p85α regulates mast cell growth, survival and cycling, we performed microarray analyses to compare the gene expression profile of MCps derived from WT and p85α-deficient mice in response to SCF stimulation. We identified 151 unique genes exhibiting altered expression in p85α-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 p85α to transcription, cell cycle, cell survival, cell adhesion, cell differentiation, and signal transduction. Our results suggest that p85α is involved in mast cell development through regulation of expression of growth, survival and cell cycle related genes.
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Subha
authors.initials: S
authors.lastname: Krishnan
authors.forename: Raghuveer Singh
authors.initials: RS
authors.lastname: Mali
authors.forename: Karl R
authors.initials: KR
authors.lastname: Koehler
authors.forename: Sasidhar
authors.initials: S
authors.lastname: Vemula
authors.forename: Anindya
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Joydeep
authors.initials: J
authors.lastname: Ghosh
authors.forename: Baskar
authors.initials: B
authors.lastname: Ramdas
authors.forename: Peilin
authors.initials: P
authors.lastname: Ma
authors.forename: Eri
authors.initials: E
authors.lastname: Hashino
authors.forename: Reuben
authors.initials: R
authors.lastname: Kapur
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016000:Cluster Analysis; D018816:Genes, cdc / Q000502:physiology*; D008407:Mast Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D019869:Phosphatidylinositol 3-Kinases / Q000145:classification / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058543:Class Ia Phosphatidylinositol 3-Kinase