Distinct promoters control transmembrane and cytosolic protein tyrosine phosphatase expression during macrophage differentiation

Abstract

We have recently isolated two cDNAs encoding two forms of transmembrane and cytosolic protein tyrosine phosphatase ε (PTPε). In this study, the 5' end of the rat PTPε gene was isolated and characterized. Transmembrane PTPε (PTPεM) and cytosolic PTPs (PTPεC) were encoded by a single gene. 5' RACE analysis and RNase protection assay showed that the mRNA of each PTPε isoform was transcribed from different promoters. The putative promoter regions of two alternative first exons lacked a TATA box, but contained potential recognition sites for several transcription factors. Reverse transcription PCR analysis revealed that PTPεC mRNA was up-regulated during interleukin 6-induced differentiation of murine leukemia M1 cells, whereas PTPεM mRNA was down-regulated. With the use of luciferase as a reporter gene, the promoter activities of the 5'-flanking regions were examined during phorbol myristate acetate-induced differentiation of HL-60 cells. In the differentiated HL-60 cells, the activity of the PTPεC promoter, but not that of PTPεM, was dramatically elevated. Furthermore, we found that PTPεC mRNA is highly expressed in mouse peritoneal macrophages and enhanced during activation by lipopolysaccharide. These results suggest that the different promoters control expression of PTε isoforms during the differentiation and/or activation of macrophages.