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

We have recently isolated two cDNAs encoding two forms of transmembrane and cytosolic protein tyrosine phosphatase epsilon (PTP epsilon). In this stud y, the 5' end of the rat PTP epsilon gene was isolated and characterized. T ransmembrane PTP epsilon (PTP epsilon M) and cytosolic PTP epsilon (PTP eps ilon C) were encoded by a single gene. 5' RACE analysis and RNase protectio n assay showed that the mRNA of each PTP epsilon isoform was transcribed fr om different promoters. The putative promoter regions of two alternative fi rst exons lacked a TATA box, but contained potential recognition sites for several transcription factors. Reverse transcription PCR analysis revealed that PTP epsilon C mRNA was up-regulated during interleukin 6-induced diffe rentiation of murine leukemia M1 cells, whereas PTP epsilon M mRNA was down regulated. With the use of luciferase as a reporter gene, the promoter acti vities of the 5'-flanking regions were examined during phorbol myristate ac etate-induced differentiation of HL-60 cells. In the differentiated HL-60 c ells, the activity of the PTP epsilon C promoter, but not that of PTP epsil on M, was dramatically elevated. Furthermore, we found that PTP epsilon C m RNA is highly expressed in mouse peritoneal macrophages and enhanced during activation by lipopolysaccharide. These results suggest that the different promoters control expression of PTP epsilon isoforms during the differenti ation and/or activation of macrophages.