Phorbol ester-induced expression, phosphorylation, and translocation of protein-tyrosine-phosphatase 1C in HL-60 cells.
PTP1C, a protein-tyrosine-phosphatase (PTP) containing two Src homology 2 domains, is expressed at high levels in HL-60 human promyelocytic leukemia cells. It represents 0.15% of total protein in a postnuclear extract and corresponds to approximately 70% of phosphatase activity measured with p-nitrophenyl phosphate at pH 5.0. Upon differentiation of HL-60 cells to macrophages induced by phorbol 12-myristate 13-acetate (PMA), the activity and expression levels of PTP1C increase 2- to 3-fold. Furthermore, PTP1C is phosphorylated on serine residues upon PMA treatment. While the enzyme localizes entirely in the cytosolic fraction in untreated cells, 30-40% is found in a particulate fraction following differentiation. Immunofluorescent staining of differentiated cells before and after digitonin treatment indicates that the bound enzyme localizes on the plasma membrane. The time courses of induction and translocation of PTP1C correlate with the differentiation process. The PMA-induced differentiation is inhibited by sodium orthovanadate, suggesting the PTPs are required for this process.
Zhao
Z
Z
Department of Biochemistry, University of Washington, Seattle 98195.
Shen
S H
SH
Fischer
E H
EH
D001692:Biological Transport; D015153:Blotting, Western; D002454:Cell Differentiation; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008264:Macrophages / Q000166:cytology / Q000201:enzymology; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D013755:Tetradecanoylphorbol Acetate