Rat alpha 1-acid glycoprotein. Gene sequence and regulation by glucocorticoids in transfected L-cells

Abstract

We have cloned and sequenced the rat gene coding for the acute phase reactant protein alpha 1-acid glycoprotein in order to determine which sequences are necessary for its regulation by glucocorticoids and which sequences are responsible for the sensitivity of this regulation to protein synthesis inhibitors. The gene contains six exons, as determined from the alpha 1-acid glycoprotein cDNA sequence, and five introns. Primer extension and S1 nuclease experiments have shown that there are two transcriptional start sites 4 base pairs apart. After cotransfection into mouse L-cells, the gene retains its inducibility by glucocorticoids, indicating that the sequences required for induction are within or around the gene. The induction of alpha 1-acid glycoprotein levels in transfected L-cells is sensitive to protein synthesis inhibitors, implying that in addition to the glucocorticoid receptor another protein(s) is necessary for full induction.