Activated protein kinase C directly phosphorylates the CD34 antigen in acute lymphoblastic leukemia cells.
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.
Sutherland
D R
DR
Oncology Clinic, Toronto Hospital, Ontario, Canada.
Fackler
M J
MJ
May
W S
WS
Matthews
K E
KE
Baker
M A
MA
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D018952:Antigens, CD34; D004789:Enzyme Activation; D005260:Female; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000201:enzymology*; D010766:Phosphorylation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018952:Antigens, CD34; D009363:Neoplasm Proteins; D011493:Protein Kinase C