title: Stat5: an essential regulator of mast cell biology.
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 Stat5, a known regulator of proliferation and survival, we investigated the effects of Stat5 deficiency on mast cell development and survival. This article will review data presented at The Fourth International Workshop on Signal Transduction in the Activation and Development of Mast Cells and Basophils. The full set of data is now in preparation for publication. We find that the absence of Stat5 A and B results in a total loss of in vivo mast cell development. Bone marrow-derived mast cell (BMMC) populations can be cultured and maintained from Stat5-deficient mice in IL-3+SCF, but not in either cytokine alone. The absence of Stat5 resulted in aberrant control of Bcl-2, Bcl-x(L) and cyclin A2, with increased apoptosis and delayed cell cycle progression after IL-3 or SCF stimulation. These results indicate that Stat5 A and B are critical regulators of in vitro and in vivo mast cell biology.
authors.affiliation: Department of Biology, Virginia Commonwealth University, Richmond, VA 23284-2012, USA. jjryan@saturn.vcu.edu
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 V
authors.initials: VV
authors.lastname: Sexl
authors.forename: Sheila R
authors.initials: SR
authors.lastname: Gillespie
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Bailey
authors.forename: Anita
authors.initials: A
authors.lastname: Gharse
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: Carlos D
authors.initials: CD
authors.lastname: Ramirez
authors.forename: Chris S
authors.initials: CS
authors.lastname: Lantz
authors.forename: John J
authors.initials: JJ
authors.lastname: Ryan
mesh_terms: D000818:Animals; D017209:Apoptosis; D015550:Cell Degranulation; D016213:Cyclins / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D007377:Interleukin-3 / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008894:Milk Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050799:STAT5 Transcription Factor; D019089:Stem Cell Factor / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
chemical_list: D016213:Cyclins; D016207:Cytokines; D004268:DNA-Binding Proteins; D007377:Interleukin-3; D008894:Milk Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; D019089:Stem Cell Factor; D015534:Trans-Activators