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

Abstract

We have recently isolated two cDNAs encoding two forms of transmembrane and cytosolic protein tyrosine phosphatase 1 (PTP1). In this study, the 5 H end of the rat PTP1 gene was isolated and characterized. Transmembrane PTP1 (PTP1M) and cytosolic PTP1 (PTP1C) were encoded by a single gene. 5 H RACE analysis and RNase protection assay showed that the mRNA of each PTP1 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 PTP1C mRNA was up-regulated during interleukin 6-induced differentiation of murine leukemia M1 cells, whereas PTP1M mRNA was downregulated. With the use of luciferase as a reporter gene, the promoter activities of the 5 H -flanking regions were examined during phorbol myristate acetate-induced differentiation of HL-60 cells. In the differentiated HL-60 cells, the activity of the PTP1C promoter, but not that of PTP1M, was dramatically elevated. Furthermore, we found that PTP1C mRNA is highly expressed in mouse peritoneal macrophages and enhanced during activation by lipopolysaccharide. These results suggest that the different promoters control expression of PTP1 isoforms during the differentiation and/or activation of macrophages.

Epidermal Growth Factor Receptor (EGFR)-mediated Positive Feedback of Protein-tyrosine Phosphatase ϵ (PTPϵ) on ERK1/2 and AKT Protein Pathways Is Required for Survival of Human Breast Cancer Cells

“…High levels of RPTP⑀, p67, and p65 proteins were observed in untreated MDA-MB-231 cells, which were modestly increased upon PMA treatment. Despite our mRNA results, we did not detect expression of cytPTP⑀ protein isoform, in consistence with previous reports showing non-overlapping protein expression of cytPTP⑀ and RPTP⑀ isoforms (8,10). Remarkably, the high basal content of RPTP⑀ in MDA-MB-231 cells correlated with high basal ERK1/2 activation (Fig.…”

Generation of novel cytoplasmic forms of protein tyrosine phosphatase epsilon by proteolytic processing and translational control

“…cyt-PTPe and tm-PTPe are identical throughout most of their sequence, including their two catalytic domains; their N-termini are, however, entirely distinct from one another, a fact which determines their unique subcellular localizations. tm-PTPe and cyt-PTPe are products of distinct mRNA species transcribed from the single PTPe gene by use of alternative promoters; the two proteins have virtually non-overlapping expression patterns in cells and among tissues, suggesting that they play distinct physiological roles (Elson and Leder, 1995a;Elson et al, 1996;Tanuma et al, 1999). As the catalytic domains of tm-PTPe and cyt-PTPe are identical, their distinct roles are believed to result from their dierent expression patterns.…”

The transmembranal and cytoplasmic forms of protein tyrosine phosphatase epsilon physically associate with the adaptor molecule Grb2

“…A second form of PTPe, known as cytoplasmic PTPe (cyt-PTPe), exists and diers from tm-PTPe only at its extreme amino terminus (Elson and Leder, 1995b). Both forms of PTPe are products of a single gene, but their disparate expression patterns suggest that each has a distinct physiological function (Elson and Leder, 1995b;Elson et al, 1996;Tanuma et al, 1999).…”