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 element present in the MIST promoter (-44 to -36) was found to bind when IC-2 mast cells were stimulated with IL-3. Mutation of this duanyu1813 element did not affect basal MIST promoter activity in P815 mast cells, but was required for activation of the MIST promoter. Furthermore, endogenous MIST gene expression was induced in mast cells by a constitutively activated form of but not by an active mutant of c-Kit receptor. These findings suggest that 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.

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