Ken & barbie selectively regulates the expression of a subset of Jak/STAT pathway target genes.

A limited number of evolutionarily conserved signal transduction pathways are repeatedly reused during development to regulate a wide range of processes. Here we describe a new negative regulator of signaling and identify a potential mechanism by which the pleiotropy of responses resulting from pathway activation is generated in vivo. As part of a genetic interaction screen, we have identified Ken & Barbie (Ken) , which is an ortholog of the mammalian proto-oncogene BCL6 , as a negative regulator of the JAK/duanyu1813 pathway. Ken genetically interacts with the pathway in vivo and recognizes a DNA consensus sequence overlapping that of in vitro. Tissue culture-based assays demonstrate the existence of Ken-sensitive and Ken-insensitive duanyu181392E binding sites, while ectopically expressed Ken is sufficient to downregulate a subset of JAK/duanyu1813 pathway target genes in vivo. Finally, we show that endogenous Ken specifically represses expression of ventral veins lacking (vvl) in the posterior spiracles. Ken therefore represents a novel regulator of JAK/duanyu1813 signaling whose dynamic spatial and temporal expression is capable of selectively modulating the transcriptional repertoire elicited by activated duanyu181392E in vivo.

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