Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, we cloned two gene fragments encoding novel protein tyrosine phosphatases, termed PTP-U1 and PTP-U2. Here, we report the full-length sequence, expression, and chromosomal localization of the PTP-U2 gene. The cDNA for PTP-U2, which was obtained from a human normal kidney library, predicts a protein of 1216 amino acids, -140 kDa, that contains a single transmembrane domain and a single intracellular catalytic domain. The extracellular domain of PTP-U2 contains 14 putative N-glycosylation sites and eight repeats of fibronectin type III-like motif. These data suggest that PTP-U2 is structurally similar to HPTP beta and DPTP10D, which have been reported previously. Northern blot analysis revealed that there were two different transcripts for PTP-U2. In kidney and brain, gene expression of PTP-U2 was detected as a 5.4 kb mRNA and in lung and placenta as 3.5 kb. The 3.5 kb transcript was also detected in human leukemia cell lines (eg., U937). Interestingly, its gene expression was enhanced by various differentiation-inducing agents, such as phorbol ester, dihydroxy vitamin D3, retinoic acid, and dimethyl sulfoxide. The bacterially expressed PTP-U2 fusion protein exhibited intrinsic tyrosine phosphatase activity. The PTP-U2 gene was assigned to chromosome 12p13.2-p13.3.
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PMID:Cloning, expression and chromosomal localization of a novel gene for protein tyrosine phosphatase (PTP-U2) induced by various differentiation-inducing agents. 775 50

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.
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PMID:Differential expression of protein tyrosine phosphatase genes during phorbol ester-induced differentiation of human leukemia U937 cells. 811 17

A large family of protein tyrosine phosphatases (PTPs) bidirectionally regulate intracellular signaling pathways by reversing agonistic or antagonistic phosphorylation events derived from the action of protein tyrosine kinases. Receptor-like PTP PTP-U2 is expressed during phorbol ester-induced differentiation of monoblastoid leukemia U937 cells. We found that the shorter isoform, PTP-U2S, was expressed at an earlier phase in the course of differentiation and the longer isoform, PTP-U2L, was induced at a later phase. In the presence of 12-O-tetradecanoylphorbol-13-acetate, ectopic expression of PTP-U2L in U937 cells enhanced several characteristics of terminally differentiated cells. Most striking was that PTP-U2L enhanced apoptosis of the differentiated cells, which was only partially inhibited by caspase inhibitor Z-Asp-CH2-DCB. The catalytically inactive mutant PTP-U2L(C --> S) still retained the ability to enhance the differentiation but retained the ability to enhance the following apoptosis of the cells to a lesser extent. These data indicate a functional involvement of PTP-U2L in apoptosis subsequent to terminal differentiation of U937 cells. Since terminally differentiated blood cells often undergo apoptosis, the data also suggest that PTP-U2L might be involved in physiological turnover of hematopoietic cells in vivo.
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PMID:Functional involvement of PTP-U2L in apoptosis subsequent to terminal differentiation of monoblastoid leukemia cells. 969 75