Transcriptional regulation of SLP-76 family hematopoietic cell adaptor MIST/Clnk by STAT5.
SLP-76-related adaptor protein MIST (also called Clnk) is expressed in a variety of cytokine-dependent hematopoietic cell lines of myeloid and lymphoid origin as well as some cytokine-independent mast cell lines. To understand the molecular mechanisms underlying the MIST gene expression, we have characterized the 5'-flanking region of the mouse MIST gene. We have identified an enhancer region (-773 to -709), which is active in P815 mast cells expressing the endogenous MIST gene, but not in EL-4 T cells lacking MIST expression. Outside of this enhancer region, one STAT element present in the MIST promoter (-44 to -36) was found to bind STAT5A when IC-2 mast cells were stimulated with IL-3. Mutation of this STAT element did not affect basal MIST promoter activity in P815 mast cells, but was required for STAT5-mediated activation of the MIST promoter. Furthermore, endogenous MIST gene expression was induced in mast cells by a constitutively activated form of STAT5A, but not by an active mutant of c-Kit receptor. These findings suggest that STAT5 is involved in cytokine-mediated up-regulation of MIST gene expression, probably in collaboration with other lineage-specific transcription factors that promote basal MIST expression in mast cells.
Sasanuma
Hiroki
H
Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan.
Tatsuno
Akiko
A
Tsuji
Kaori
K
Hidano
Shinya
S
Morita
Sumiyo
S
Kitamura
Toshio
T
Kubo
Masato
M
Kitamura
Daisuke
D
Goitsuka
Ryo
R
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008894:Milk Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017510:Protein Folding; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D050799:STAT5 Transcription Factor; D013601:T-Lymphocytes / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C488191:Clnk protein, mouse; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C092947:SLP-76 signal Transducing adaptor proteins; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; D015534:Trans-Activators