Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polymerase chain reaction (PCR) was used to identify protein-tyrosine phosphatases (PTPases) in a human leukemic cell line, F-36P. Degenerate primers deduced from the highly conserved amino acid sequences in the catalytic domain of known PTPases were used for amplification. Among 16 clones sequenced, 13 were identical to known PTPases, whereas the other three clones were disclosed to encode novel PTPases. The expression pattern of one of the three newly identified PTPases, designated as F-36-12, was further analysed. In murine tissues, the F-36-12 message was predominantly expressed in brain, kidney, and intestine, and was weakly expressed in heart and thymus. In human hematopoietic cell lines, the F-36-12 message was preferentially expressed in a promyelocytic leukemic cell line, HL60, and two factor-dependent leukemic cell lines, F-36P and F-36E, that are dependent on granulocyte-macrophage colony-stimulating factor or interleukin-3 and erythropoietin, respectively. The transcript was approximately 8 kb long and the message level in HL60 cells was slightly increased at 24 hours and then slowly declined when treated with dimethyl sulfoxide for granulocyte differentiation, while the message level was rapidly decreased when treated with 12-O-tetradecanoylphorbol 13-acetate for monocyte/macrophage differentiation. These results show that several PTPases including three novel ones are expressed in a human leukemic cell line and that the particular PTPase, F-36-12, might be involved in the differentiation process in HL60 cells.
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PMID:Identification of novel protein-tyrosine phosphatases in a human leukemia cell line, F-36P. 848 28

Phosphotyrosine phosphatases (PTPases) regulate cellular metabolic activation by reversing the effects of tyrosine kinases activated earlier in intracellular signaling pathways. We coupled fluorescence-activated cell sorter analysis using anti-CD45 monoclonal antibody with direct measurements of enzyme activity in resolved subcellular fractions to define mechanisms that potentially regulate the availability and activity of CD45-PTPase on neutrophil plasma membranes. Neutrophils in freshly obtained blood as well as neutrophils freshly isolated from blood were found to possess detectable levels of plasma membrane CD45 as assessed by immunofluorescence. However, plasma membranes from these cells were essentially devoid of PTPase catalytic activity, which was largely confined to the specific granules. Granulocyte-macrophage colony-stimulating factor (GM-CSF) upregulated both the catalytic and antigenic components of CD45-PTPase on the plasma membrane of these cells. Upregulation was associated with a shift in the particulate subcellular PTPase catalytic activity from the specific granule fraction to the plasma membrane fraction. The tyrosine kinase inhibitor genistein abrogated GM-CSF-promoted upregulation of plasma membrane CD45 PTPase but did not prevent the GM-CSF-dependent decrease in specific granule catalytic activity. Anti-CD45 antibody immunoprecipitated PTPase activity from both specific granules of resting cells and plasma membranes of GM-CSF-treated cells. However, antiphosphotyrosine immunoprecipitated only activity that had translocated to the plasma membrane, suggesting a role for CD45 phosphorylation in translocation. Western analysis confirmed the tyrosine phosphorylation of CD45 in plasma membranes of GM-CSF-treated neutrophils. Preincubation of plasma membranes of GM-CSF-stimulated neutrophils with cytosol from resting cells resulted in a time- and temperature-dependent loss in membrane PTPase as a consequence of the effects of a cytosolic inactivator. Cytosol obtained from stimulated neutrophils possessed substantially reduced levels of this PTPase inactivator. We conclude that activity of the catalytic component of membrane PTPase in circulating neutrophils is regulated by a cytosolic inactivator. Upon stimulation, intact CD45 PTPase is incorporated into the plasma membrane by a process that requires tyrosine phosphorylation. As a result of inhibition of the cytosolic inactivator, the translocated PTPase expresses full activity, thereby amplifying the potential regulatory influence of the enzyme on the cells' functional response.
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PMID:Cytosolic inactivation of translocated neutrophil plasma membrane protein tyrosine phosphatase. 854 61