Regulation of CD45 expression in human leukemia cells.
The CD45 antigen cluster identifies a family of transmembrane glycoprotein tyrosine phosphatases (PTPases) present on nearly all hemopoietic cells. Recent studies suggest that CD45 may play a role in the control of receptor mediated blood cell responses, and that expression of the CD45 gene varies during bone marrow cell maturation. However, relatively little is known of the mechanisms controlling CD45 expression and function. Here we show that the induction of granulocyte or monocyte differentiation of HL60 leukemia cells is accompanied by a rapid increase in CD45 antigen expression and CD45 PTPase activity. In contrast, other leukemia cell lines induced for monocyte/macrophage differentiation did not show increased CD45. Immunoprecipitation of radiolabelled CD45 glycoprotein from dimethyl sulphoxide (DMSO) treated HL60 cells indicated that the cells expressed 200 and 180 kD isoforms. Northern blots of steady-state RNA from HL60 cells showed a 4-11-fold increase in CD45 transcripts after DMSO treatment, but no alteration in the half-life of CD45 mRNA. Nuclear transcription assays showed that CD45 expression was controlled at the level of gene transcription. Namalwa Burkitt leukemia cells expressing the heterologous epidermal growth factor (EGF) receptor protein tyrosine kinase were used to assess the specificity of CD45 PTPase activity. Co-clustering of CD45 and the EGF receptor with specific monoclonal antibodies failed to alter the EGF stimulated tyrosine phosphorylation of the EGF receptor. These studies indicate that CD45 increases during myeloid maturation, and the expression of the CD45 gene is controlled at the level of gene transcription. Preliminary studies suggest that CD45 does not alter the protein tyrosine kinase activity of the EGF receptor in intact cells, suggesting substrate specificity in vivo.
Taetle
R
R
Division of Hematology/Oncology, University of California, San Diego.
Ostergaard
H
H
Smedsrud
M
M
Trowbridge
I
I
D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic / Q000502:physiology*; D006649:Histocompatibility Antigens / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D017493:Leukocyte Common Antigens; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000943:Antigens, Differentiation; D006649:Histocompatibility Antigens; D066246:ErbB Receptors; D010749:Phosphoprotein Phosphatases; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases; D004121:Dimethyl Sulfoxide