Expression analysis and modulation by HIV-Tat of the tyrosine phosphatase HD-PTP

The human immunodeficiency virus type 1 Tat transactivates viral proteins and also affects the expression of eukaryotic genes. Since Tat is angiogenic, we assumed that the isolation of differentially expressed genes in Tat-treated endothelial cells would yield insights into the molecular mechanisms of the angiogenic process. By RNA fingerprinting, we found that Tat upregulates the tyrosine phosphatase HD-PTP mRNA in a human endothelial cell line. At the moment, little is known about HD-PTP. We here show that HD-PTP is highly conserved through evolution from yeast to man, and is ubiquitously distributed in adult and fetal tissues. HD-PTP is expressed in human cell lines derived from different tumors, but the mRNA levels do not appear to correlate with the malignant phenotype of the cells. HD-PTP mRNA was also detected in cell lines derived from tumors that develop in BKV/Tat-transgenic mice. Interestingly, a relation exists between the amounts of secreted Tat and the levels of HD-PTP mRNA. HD-PTP encodes a 185-kDa protein which is expressed in human endothelial from the umbilical cord and in human Kaposi-spindle cells. Tat-induction of HD-PTP mRNA parallels only with a slight increase of the protein, which occurs after 24 and 48 h of incubation in the presence of Tat. These results suggest that HD-PTP amounts might be regulated both at the transcriptional and post-transcriptional levels.