Expression of CD45 Alters Phosphorylation of the lck-Encoded Tyrosine Protein Kinase in Murine Lymphoma T-Cell Lines

• Published in: Proceedings of the National Academy of Sciences - PNAS 1989-11, Vol.86 (22), p.8959-8963
• Main Authors: Ostergaard, Hanne L., Shackelford, Deborah A., Hurley, Tamara R., Johnson, Pauline, Hyman, Robert, Sefton, Bartholomew M., Trowbridge, Ian S.
• Format: Article
• Language: English
• Subjects: Amino acids; Analytical, structural and metabolic biochemistry; Animals; Antibodies; Antigens, Differentiation - genetics; Antigens, Differentiation - immunology; Biological and medical sciences; CD45 antigen; Cell Line; Cell lines; Cellular immunity; Fundamental and applied biological sciences. Psychology; Gene Expression; Glycoproteins; Histocompatibility Antigens - genetics; Histocompatibility Antigens - immunology; Immunoblotting; Kinetics; Leukocyte Common Antigens; Lymphocyte Activation; lymphocytes T; Lymphoma; Lymphoma - enzymology; Lymphoma - immunology; Membrane Glycoproteins - genetics; Mice; Mutation; Peptide Fragments - isolation & purification; Phosphatases; Phosphorylation; Protein isoforms; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Proteins; T lymphocytes; T-Lymphocytes - enzymology; T-Lymphocytes - immunology; Trypsin
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.22.8959

CD45 is a family of high molecular weight leukocyte cell surface glycoproteins. Recently, two related subregions of the cytoplasmic domain of CD45 have been shown to have 30-40% amino acid identity with a human placental protein phosphotyrosine phosphatase, and CD45 isolated from human spleen was found to exhibit intrinsic protein phosphotyrosine phosphatase (EC 3.1.3.48) activity. In the present studies, we demonstrate that each of the known isoforms of murine CD45 has an equivalent basal level of protein phosphotyrosine phosphatase activity and establish that this enzymatic activity is associated with the cytoplasmic domain of the glycoprotein. Studies with three independent sets of well-characterized parental CD45+, mutant CD45-, and revertant CD45+ lymphoma cell lines indicate that loss of CD45 increases the phosphorylation of the src-related leukocyte-specific tyrosine protein kinase p56lck on tyrosine-505, a putative negative regulatory site. This suggests that CD45 may play a role in leukocyte growth regulation by altering the kinase activity of p56lck.