title: Stat5 expression is critical for mast cell development and survival.
abstract: Interleukin-3 (IL-3) and stem cell factor (SCF) are important mast cell growth and differentiation factors. Since both cytokines activate the transcription factor signal transducer and activator of transcription 5 (Stat5), a known regulator of proliferation and survival, we investigated the effects of Stat5 deficiency on mast cell development and survival. Bone marrow-derived mast cell (BMMC) populations cultured from Stat5A/B-deficient mice survived in IL-3 + SCF, but not in either cytokine alone. These cells demonstrated reduced expression of Bcl-2, Bcl-x(L), cyclin A2, and cyclin B1, with increased apoptosis and delayed cell cycle progression during IL-3 or SCF culture. Finally, the absence of Stat5 resulted in loss of in vivo mast cell development, as judged by assessments of Stat5-deficient mice and transplantation of Stat5-deficient bone marrow cells to mast cell-deficient recipient mice. These results indicate that Stat5A and Stat5B are critical regulators of in vitro and in vivo mast cell development and survival.
authors.affiliation: Department of Biology, Virginia Commonwealth University, Richmond, VA 23284-2012, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Shelburne
authors.forename: Margaret E
authors.initials: ME
authors.lastname: McCoy
authors.forename: Roland
authors.initials: R
authors.lastname: Piekorz
authors.forename: Veronica
authors.initials: V
authors.lastname: Sexl
authors.forename: Kwan-Ho
authors.initials: KH
authors.lastname: Roh
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Jacobs-Helber
authors.forename: Sheila R
authors.initials: SR
authors.lastname: Gillespie
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Bailey
authors.forename: Paria
authors.initials: P
authors.lastname: Mirmonsef
authors.forename: Meredith N
authors.initials: MN
authors.lastname: Mann
authors.forename: Mohit
authors.initials: M
authors.lastname: Kashyap
authors.forename: Harry V
authors.initials: HV
authors.lastname: Wright
authors.forename: Hey Jin
authors.initials: HJ
authors.lastname: Chong
authors.forename: L Andrew
authors.initials: LA
authors.lastname: Bouton
authors.forename: Brian
authors.initials: B
authors.lastname: Barnstein
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Ramirez
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Bunting
authors.forename: Steven
authors.initials: S
authors.lastname: Sawyer
authors.forename: Chris S
authors.initials: CS
authors.lastname: Lantz
authors.forename: John J
authors.initials: JJ
authors.lastname: Ryan
mesh_terms: D000818:Animals; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D004789:Enzyme Activation / Q000235:genetics; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008894:Milk Proteins; D008928:Mitochondria / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019089:Stem Cell Factor / Q000494:pharmacology; D015534:Trans-Activators / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
chemical_list: D016213:Cyclins; D004268:DNA-Binding Proteins; D007377:Interleukin-3; D008894:Milk Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D019089:Stem Cell Factor; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D020169:Caspases