Signaling complex formation of CD44 with src-related kinases.
The complex formation of murine CD44 with the src-like protein tyrosine kinases, lck and lyn, was investigated. In accordance with previous observations, stable CD44-lck and CD44-lyn complexes were detected in nonstimulated lymphoid T- and B-cells, respectively. In addition, a direct modulation of lck and lyn by CD44 was observed as revealed by the CD44-dependent translocation of these enzymes to the Triton X-100 resistant cell fraction. To clarify which receptor domain is responsible for the association, peptide binding assays were performed. Interestingly, the synthetic peptide pCD44 (ILAVCIAVNSRRR), which corresponds to the plasma membrane-cytoplasmic interface region of murine CD44, exhibited a high capacity to bind lck and lyn. A single amino acid modification in the position of the cysteine residue completely abolished this interaction, while the truncation of the three tandem arginines significantly decreased it. Remarkably, similar sequences were found in a number of other molecules including subunits of receptors recognizing antigens, immunoglobulins, extracellular matrix components, accessory molecules, cytokines and also in certain viral gene products. Synthetic peptides corresponding to the homologous regions found in CD28 and FcepsilonRIbeta were also studied and comparable lck-lyn-binding potentials were detected. These data suggest a novel interaction between src-family kinases and CD44, CD28, FcepsilonRIbeta, and provide a simple model for the association of src-like kinases with transmembrane proteins.
Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg. zoltan.rozsnyay@wl.com
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D000595:Amino Acid Sequence; D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism; D002451:Cell Compartmentation / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D018960:Hyaluronan Receptors / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D006825:Hybridomas; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D046911:Macromolecular Substances; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D017455:Receptors, IgE / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology
D018106:CD28 Antigens; D018960:Hyaluronan Receptors; D046911:Macromolecular Substances; D010455:Peptides; D017455:Receptors, IgE; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases