Persistent superphosphorylation of leukosialin (CD43) in activated T cells and in tumour cell lines.
CD43 (leukosialin) is a highly sialylated, single-chain molecule expressed on most human leucocytes. Regulatory signals appear to be transduced through the molecule as suggested by the ability of anti-CD43 antibodies to induce aggregation and proliferation of T cells and to enhance B-cell proliferation and natural killer cell activity. Activation of protein kinases is an essential event in signal transduction. We were therefore interested to study whether CD43 may function as a substrate for protein kinases during mitogenic activation of lymphocytes. We show that CD43 was rapidly superphosphorylated (within minutes) on serine residues following addition of phorbol ester (PMA) to peripheral blood lymphocytes. PMA treatment of the cells was not followed by rapid down-regulation of CD43. Activation of the lymphocytes by concanavalin A or anti-CD3 antibodies (OKT-3) also resulted in superphosphorylation of CD43. However, the phosphorylation was delayed as compared to that induced by PMA and was detected 3-4 h after the addition of the reagents. A plateau was reached after 24-48 h of stimulation. Interestingly, the high level of phosphorylation of CD43 was maintained in long-term cultures of T cells activated by various means. Furthermore, CD43 was found to be constitutively superphosphorylated (on serine and tyrosine) in continuously growing cell lines of T, B, and non-lymphoid origin. Taken together, the results suggest that CD43 has an important role during both early and late phases of T-cell activation and that modulation of its biochemical properties by protein kinases may be associated with progression through the cell cycle and with cellular growth.
Axelsson
B
B
Department of Immunology, University of Stockholm, Sweden.
Perlmann
P
P
D015703:Antigens, CD / Q000378:metabolism*; D006801:Humans; D051917:Leukosialin; D008213:Lymphocyte Activation; D010766:Phosphorylation; D011487:Protein Conformation; D012795:Sialoglycoproteins / Q000032:analysis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D051917:Leukosialin; C465014:SPN protein, human; D012795:Sialoglycoproteins; D013755:Tetradecanoylphorbol Acetate