Differential expression of protein tyrosine phosphatase genes during phorbol ester-induced differentiation of human...

Some human leukemia cell lines, such as HL-60 and U937, differentiate to monocyte/macrophage by treatment with chemicals such as phorbol ester or 1,25-dihydroxy vitamin D3. In this report, we demonstrate that cellular protein tyrosine phosphatase (PTPase) activity (especially in cytosol) in monoblastoid leukemia U937 cells increased up to 2-fold during the course of monocytic differentiation. We have cloned 13 PTPase-related gene fragments from the differentiated U937 cells using the reverse transcription-polymerase chain reaction method. Two of these were found to be genes of novel isozymes, PTP-U1 and PTP-U2. We investigated the changes in expression of each isozyme during the differentiation of the cells and found that nine isozymes (both cytosolic and transmembranous) were expressed more in the differentiated cells than in the undifferentiated cells. Among them, PTP-U1 and PTP-U2 were greatly induced by phorbol ester. Interestingly, there were two cytosolic isozymes that were down-regulated during the course of differentiation. Our present data suggest that the functions of the PTPase isozyme during monocytic maturation are not always equivalent to each other, and tyrosine dephosphorylation may participate in several different pathways of signal transduction during the differentiation of leukemia cells.