ALTERNATIVE PROMOTER USAGE OF THE FOS-RESPONSIVE GENE FIT-1 GENERATESMESSENGER-RNA ISOFORMS CODING FOR EITHER SECRETED OR MEMBRANE-BOUND PROTEINS RELATED TO THE IL-1 RECEPTOR

Fit-1 has been identified previously as a Fos-responsive gene of rat f ibroblasts. Here we show that Fit-1 is directly regulated by the estro gen-inducible transcription factor Fos-ER and that it belongs to the f amily of delayed early genes. Two different mRNA isoforms are expresse d from the Fit-1 gene. The Fit-1M mRNA isolated from spleen codes for a membrane-bound protein which is most closely related in its extracel lular, transmembrane and intracellular domains to the type I interleuk in-1 (IL-1) receptor. The Fit-1S mRNA of fibroblasts directs, instead, the synthesis of a secreted protein consisting of only the extracellu lar domain. Analysis of the exon-intron structure of the Fit-1 gene in dicated that the Fit-1S and Fit-1M mRNAs are transcribed from two diff erent promoters and that the sequence differences at their 3' ends res ult from alternative 3' processing. Northern blot analysis with specif ic 5' and 3' probes directly demonstrated tight coupling between alter native promoter usage and 3' processing of the Fit-1 transcripts. The orthologous gene of the mouse (known as T1 or ST2) is expressed during ontogeny first in the fetal liver of the embryo and then in lung and hematopoietic tissues of the adult. The mRNA coding for the membrane-b ound protein is more abundantly expressed in all of these tissues, whi le the transcript for the secreted form predominates in fibroblasts an d mammary epithelial cells. Differential regulation of two distinct pr omoters is thus used to determine the ratio between secreted and membr ane-bound forms of Fit-1 (T1/ST2) which may modulate signaling in resp onse to IL-1.