AbstractThe 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. J. Cell. Biochem. 98: 301–308, 2006. © 2006 Wiley‐Liss, Inc.