Prorein-tyrosine phosphorylation and dcphosphorylntion are directly associated with cellular growlh. signal transduction, and ncoplastic trnnsformation. Here we report the isolation of a complementary DNA @DNA) clone encoding a novel protein-tyrosinc phosphatasc (PTP) from a human T cell PEER cDNA library. The predicted open reading frame encodes a -68.kDa protein composed of 593 amino acids which contains LWO src-homology region 2's (SH2 domains) at the N terminus; this PTP is dcsibflated as SH-PTP3. Northern blot analysis revealed that SH-PTP3 mRNA was expressed throughout many tissues and the transcriptional size wns consistent al about 6.0 kb. As with olhcr SH2 domains in x-family kinascs, the SH2 domains of SH-PTP3 may play a crucial role in interactions with tyrosinc phosphorylnlcd signding proteins, including itself and protein tyrosine kinascs (PTKs), to regulute targets' enzyme activity.Protein-tyrosine phosphatasc; Protein lyrosine kinase; src-Homology region 2

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The putative Wilms' tumor-suppressor gene (wt1) encodes a zinc finger DNA binding protein that functions as a transcription repressor. The wt1 gene expression corresponds to kidney development, suggesting a role for this gene in nephroblast differentiation. Here we show that wt1 mRNA expression was downregulated during terminal differentiation of promyelocytic HL60 cells. When HL60 cells were induced to differentiate to granulocytes by dimethyl sulfoxide (DMSO) or retinoic acid (RA), a marked downregulation in the levels of wt1 transcripts was found. The wt1 transcripts were also downregulated in HL60 cells during differentiation to monocytes by vitamin D3 or 12-o-tetradecanoyl- phorbol-13-acetate. Nuclear run-on transcription studies showed the transcriptional rate of wt1 gene was not significantly altered during DMSO-induced granulocytic differentiation, suggesting the downregulation was mostly caused by posttranscriptional modification. Importantly, wt1 transcripts were not significantly altered in K562 cells by treatments with DMSO or RA, which do not induce differentiation of K562 cells. These findings suggest that wt1 gene expression may be downregulated as a differentiation-linked event in HL60 cells.

Histone deacetylase (HDAC) inhibitors can induce transcriptional activation of a number of genes and induce cellular differentiation as histone acetylation levels increase. Although these inhibitors induce apoptosis in several cell lines, the precise mechanism by which they do so remains obscure. This study shows that HDAC inhibitors, sodium butyrate and trichostatin A (TSA), abrogate interleukin (IL)-2–mediated gene expression in IL-2–dependent cells. The HDAC inhibitors readily induced apoptosis in IL-2–dependent ILT-Mat cells and BAF-B03 transfectants expressing the IL-2 receptor βc chain, whereas they induced far less apoptosis in cytokine-independent K562 cells. However, these inhibitors similarly increased acetylation levels of histones in both cells. Although histone hyperacetylation is believed to lead to transcriptional activation, the results showed an abrogation of IL-2–mediated induction of c-myc,bag-1, and LC-PTP gene expression. This observed abrogation of gene expression occurred prior to phosphatidylserine externalization, a process that occurs in early apoptotic cells. Considering the biologic role played by IL-2–mediated gene expression in cell survival, these data suggest that its abrogation may contribute to the apoptotic process induced by HDAC inhibitors.