RRC ID 1393
Author Sasanuma H, Tatsuno A, Tsuji K, Hidano S, Morita S, Kitamura T, Kubo M, Kitamura D, Goitsuka R.
Title Transcriptional regulation of SLP-76 family hematopoietic cell adaptor MIST/Clnk by STAT5.
Journal Biochem. Biophys. Res. Commun.
Abstract 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.
Volume 321(1)
Pages 145-53
Published 2004-8-13
DOI 10.1016/j.bbrc.2004.06.126
PII S0006-291X(04)01422-6
PMID 15358227
MeSH Adaptor Proteins, Signal Transducing Animals Base Sequence Carrier Proteins / genetics* Cell Line DNA-Binding Proteins / metabolism* Mast Cells / physiology* Mice Milk Proteins / metabolism* Molecular Sequence Data Phosphoproteins / metabolism* Polymerase Chain Reaction Protein Folding RNA, Messenger / genetics Restriction Mapping STAT5 Transcription Factor T-Lymphocytes / physiology Trans-Activators / metabolism* Transcription, Genetic / genetics* Transcriptional Activation
IF 2.559
Times Cited 2
Human and Animal Cells IC-2