Induction of protein-tyrosine-phosphatase activity by interleukin 6 in M1 myeloblastic cells and analysis of possible counteractions by the BCR-ABL oncogene.
Interleukin 6 (IL-6) induces in M1 myeloblastic cells growth arrest and terminal differentiation toward monocytes. It is reported here that IL-6 reduced by 5- to 20-fold the tyrosine phosphorylation of cellular proteins in these cells. The same-fold reduction was also observed in M1 cells that were transfected with the BCR-ABL deregulated protein kinase. In these stable clones, the levels of tyrosine phosphorylation of cellular proteins were 30- to 100-fold higher than in the parental cells. IL-6 did not reduce the expression levels or the inherent tyrosine kinase activity of BCR-ABL p210. By measuring the protein-tyrosine-phosphatase (PTPase; protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48) activity in crude cell lysates, we found that protein dephosphorylation resulted, at least partially, from induction of PTPase activity by IL-6. The induction of PTPase in the BCR-ABL-transfected clones was not sufficient to confer the minimal protein phosphorylation levels characteristic of IL-6-treated cells. Yet, the transfected M1 clones showed normal growth and differentiation responses to IL-6. None of the gene responses to IL-6 including suppression in the levels of c-myc, c-myb, and cyclin A mRNA; junB and c-jun mRNA induction; and dephosphorylation of retinoblastoma protein were rescued by the BCR-ABL oncogene. The functional relevance of PTPase induction by IL-6 is discussed.
Zafriri
D
D
Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
Argaman
M
M
Canaani
E
E
Kimchi
A
A
D016213:Cyclins / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D015850:Interleukin-6 / Q000494:pharmacology*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000201:enzymology*; D015513:Oncogene Proteins / Q000378:metabolism; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis*; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D013347:Subcellular Fractions / Q000201:enzymology; D013489:Suppression, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D016213:Cyclins; D015850:Interleukin-6; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; D017027:Protein Tyrosine Phosphatases