ACTIVATED PROTEIN-KINASE-C DIRECTLY PHOSPHORYLATES THE CD34 ANTIGEN IN ACUTE LYMPHOBLASTIC-LEUKEMIA CELLS

被引:10
作者
SUTHERLAND, DR
FACKLER, MJ
MAY, WS
MATTHEWS, KE
BAKER, MA
机构
[1] Oncology Clinic, Toronto Hospital, Ontario
[2] Johns Hopkins Oncology Center, Baltimore, MD
关键词
CD34; ANTIGEN; PHOSPHOPROTEIN; PROTEIN KINASE-C; PHOSPHORYLATION; ACUTE LYMPHOBLASTIC LEUKEMIA;
D O I
10.3109/10428199209051012
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The precursors of all blood cell lineages are contained within the 1-3% of bone marrow cells which express the CD34 antigen, and this population can reconstitute the hematopoietic system of lethally irradiated animals and humans. A potential regulatory role for the CD34 antigen in progenitor cell function and differentiation was indicated by our recent findings that the CD34 antigen can be phosphorylated in vivo to high stoichiometry in primitive CD34+ cell-lines by activated protein kinase C. To exclude the possibility that these effects were restricted to cell-lines, we have performed similar experiments on fresh cells from a patient with drug-resistant acute lymphoblastic leukemia. Similar to our previous findings, we found the CD34 antigen to be hyperphosphorylated in lymphoblasts labeled in the presence of active phorbols. The same peptides which were hyperphosphorylated in phorbol-stimulated cell-lines were also phosphorylated in phorbol-stimulated lymphoblasts. These data indicate that CD34 is a substrate molecule for PKC in fresh CD34+ lymphoblasts and underline the role of modulators of PKC activity in the biology of primitive leucocytes.
引用
收藏
页码:337 / 344
页数:8
相关论文
共 41 条
[1]  
Civin C., Strauss L.C., Brovall C., Fackler M.J., Schwartz J.F., Shaper J.H., Antigenic analysis of hematopoiesis III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG1 a cells, J Immunol., 133, pp. 157-165, (1984)
[2]  
Katz F., Tindle R.W., Sutherland D.R., Greaves M.F., Identification of a membrane glycoprotein associated with hemopoietic progenitor cells, Leuk. Res, 9, pp. 191-198, (1985)
[3]  
Andrews R.G., Singer J.W., Bernstein I.D., Monoclonal antibody 12.8 recognizes a 115-kd molecule present on both unipotent and multipotent colony-forming cells and their precursors, Blood, 67, pp. 842-845, (1986)
[4]  
Ryan D., Kossover S., Mitchell S., Frantz C., Hennessey L., Cohen H.J., Subpopulations of common acute lymphoblastic leukemia antigen-positive lymphoid cells in normal bone marrow identified by hematopoietic differentiation antigens, Blood, 68, pp. 417-425, (1986)
[5]  
Schuh A., Sutherland D.R., Horsfall W., Mills G.B., DubE I., Baker M.A., Keating A., Chronic myelogenous leukaemia arising in a progenitor common to T cells and myeloid cells, Leukaemia, 4, pp. 631-636, (1990)
[6]  
Fackler M.J., Civin C.I., Sutherland D.R., Baker M.A., May W.S., Activated Protein Kinase C directly phosphorylates the CD34 antigen on hematopoietic Cells, J. Biol. Chem., 265, pp. 11056-11061, (1990)
[7]  
Andrews R.G., Singer J.W., Bernstein I.D., Human hematopoietic precursors in long-term culture: single CD34 + cells that lack detectable T cell, B cell, and myeloid cell antigens produce multiple colony-forming cells when cultured with marrow stromal cells, J. Exp. Med., 172, pp. 355-358, (1990)
[8]  
Berenson R.J., Andrews R.G., Bensinger W.I., Kalamasz D., Knitter G., Buckner C.D., Bernstein I.D., Antigen CD34-positive marrow cells engraft lethally irradiated baboons, J. Clin. Invest., 81, pp. 951-955, (1988)
[9]  
Wagermaker G., Van Gils F.C.J.M., Bart-Baumeister J.A.K., Weilenger J.J., Levinsky R.J., Sustained engraftment of allergenic CD34 positive hemopoietic stem cells in rhesus monkeys, Exp Hematol., 18, (1990)
[10]  
Berenson R.J., Bensinger W.I., Hill R.S., Andrews R.G., Garcia-Lopez J., Kalamaz D.F., Still B.J., Spitzer G., Buckner D., Bernstein I.D., Thomas E.D., Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma, Blood, 77, pp. 1717-1722, (1991)