Changes in the phosphorylation status of a 19 kD cytosolic protein are linked to the growth arrest of HL-60 cells.
A major 19 kD cytosolic protein (p19) has been described in a number of cell systems with respect to its rapid phosphorylation when protein kinase C is activated and has been proposed as a key substrate of this enzyme. Phosphorylation of p19 occurs when the growth of cells is affected by 12-O-tetradecanoylphorbol-13-acetate (TPA) and it has been proposed that increased phosphorylation of p19 relates to the cessation of cell growth. This study delineates precisely the relationship between p19 phosphorylation changes in the growth and differentiation status of cells. Changes in the levels of two phosphorylated forms of p19 were assessed in HL-60 promyelocytic cells and a variant HL-60 cell line which stopped growing and differentiated in response to TPA and were compared to changes seen in HL-60 variant lines which merely growth arrested when treated with TPA. In lines which either did or did not differentiate, in response to TPA, the p19 protein was rapidly and transiently phosphorylated. Thus, this alteration in the phosphorylation status of p19 is associated with the process of growth arrest and not related to the onset of cell differentiation. The p19 protein and the enzymes which effect its phosphorylation status modulate the growth of cells and possible disregulation of p19 and/or its kinases and phosphatases is of interest as regards the leukaemic transformation of cells.
Jones
N A
NA
Department of Immunology, Medical School, University of Birmingham, U.K.
Lord
J M
JM
Brown
G
G
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology; D008868:Microtubule Proteins; D009363:Neoplasm Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D050777:Stathmin; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D008868:Microtubule Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; C493995:STMN1 protein, human; D050777:Stathmin; D013755:Tetradecanoylphorbol Acetate