Hyaluronan binding by CD44 is regulated by a phosphorylation-independent mechanism

Authors

  • Caroline R. Uff,

    Corresponding author
    1. Department of Biology, Imperial College of Science, Technology and Medicine, London, GB
    • Department of Biology, Imperial College of Science, Technology and Medicine, Prince Consort Road, London SW7 2BB, GB Fax: 01 71-5 84-20 56
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  • Stephen J. Neame,

    1. Department of Biology, Imperial College of Science, Technology and Medicine, London, GB
    Current affiliation:
    1. Eisai London Research Laboratories Ltd., Bernard Katz Building, University College London, Gower Street, London WC1E 6BT, GB
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  • Clare M. Isacke

    1. Department of Biology, Imperial College of Science, Technology and Medicine, London, GB
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Abstract

CD44 is an adhesion receptor for which the major characterized ligand is the extracellular matrix glycosaminoglycan, hyaluronan. This interaction underlies CD44-mediated cell attachment, cell migration, and matrix remodelling during development and wound healing. Truncation of the CD44 cytoplasmic domain does not prevent cell surface expression of this hyaluronan receptor but it dramatically impairs ligand binding. In this study we have examined the role of phosphorylation in regulating this function by mutating the target serine residues to either neutral amino acids with the aim of creating a phosphorylation-incompetent molecule, or to acidic residues to mimic a fully phosphorylated CD44. In transfected AKR1 cells the behavior of both the neutral and acidic mutants was indistinguishable from wild-type CD44, indicating that there is a phosphorylation-independent mechanism involved in regulating hyaluronan binding.

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