Stat5: an essential regulator of mast cell biology.
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.
Shelburne
Christopher P
CP
Department of Biology, Virginia Commonwealth University, Richmond, VA 23284-2012, USA. jjryan@saturn.vcu.edu
McCoy
Margaret E
ME
Piekorz
Roland
R
Sexl
Veronica V
VV
Gillespie
Sheila R
SR
Bailey
Daniel P
DP
Gharse
Anita
A
Mirmonsef
Paria
P
Mann
Meredith N
MN
Kashyap
Mohit
M
Wright
Harry V
HV
Chong
Hey Jin
HJ
Bouton
L Andrew
LA
Ramirez
Carlos D
CD
Lantz
Chris S
CS
Ryan
John J
JJ
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*
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