Association of 75/80-kDa phosphoproteins and the tyrosine kinases Lyn, Fyn, and Lck with the B cell molecule CD20. Evidence against involvement of the cytoplasmic regions of CD20.
CD20, a non-glycosylated cell-surface protein expressed exclusively on B lymphocytes, is one of a family of 4-pass transmembrane molecules that also includes the beta chain of the high affinity receptor for IgE. The precise function of CD20 is unknown, although in vitro effects of CD20-specific antibodies on resting B cells ... indicate that it is able to transduce an extracellular signal affecting the G0/G1 cell cycle transition. Previous studies have demonstrated that CD20-initiated intracellular signals involve tyrosine kinase activation and that CD20 is tightly associated with both serine and tyrosine kinases. Here, analysis of CD20-associated molecules has revealed that CD20 is associated with the Src family tyrosine kinases p56/53lyn, p56lck, and p59fyn and with 75/80-kDa proteins phosphorylated in vivo on tyrosine residues. Mutagenesis of CD20 was performed to define regions of CD20 involved in intermolecular interactions. Mutants were analyzed in the human T lymphoblastoid cell line Molt-4, in which ectopically expressed wild-type CD20 associated with p59fyn, p56lck, and 75/80-kDa phosphoproteins. Deletion of major portions of the cytoplasmic regions of CD20 did not abolish its association with either p75/80 or tyrosine kinases. The interaction between CD20 and the Src-related kinases is therefore likely to be independent of CD20 cytoplasmic domains and may occur indirectly. The interaction may be mediated by the p75/80 phosphoproteins, which were found to be tightly associated with the Src family kinases isolated from the CD20 complex.
Mesh Terms:
Amino Acid Sequence, Antigens, CD, Antigens, CD20, Antigens, Differentiation, B-Lymphocyte, B-Lymphocytes, Base Sequence, Cells, Cultured, Cytoplasm, DNA Primers, Enzyme Precursors, Humans, Intracellular Signaling Peptides and Proteins, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Macromolecular Substances, Molecular Sequence Data, Phosphoproteins, Phosphotyrosine, Precipitin Tests, Protein Binding, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fyn, Sequence Deletion, T-Lymphocytes, Transfection, Tyrosine, src-Family Kinases
Amino Acid Sequence, Antigens, CD, Antigens, CD20, Antigens, Differentiation, B-Lymphocyte, B-Lymphocytes, Base Sequence, Cells, Cultured, Cytoplasm, DNA Primers, Enzyme Precursors, Humans, Intracellular Signaling Peptides and Proteins, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Macromolecular Substances, Molecular Sequence Data, Phosphoproteins, Phosphotyrosine, Precipitin Tests, Protein Binding, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fyn, Sequence Deletion, T-Lymphocytes, Transfection, Tyrosine, src-Family Kinases
J. Biol. Chem.
Date: Sep. 22, 1995
PubMed ID: 7545683
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