title: Hyaluronan binding by CD44 is regulated by a phosphorylation-independent mechanism.
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.
authors.affiliation: Department of Biology, Imperial College of Science, Technology and Medicine, London, GB.
authors.forename: C R
authors.initials: CR
authors.lastname: Uff
authors.forename: S J
authors.initials: SJ
authors.lastname: Neame
authors.forename: C M
authors.initials: CM
authors.lastname: Isacke
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D006801:Humans; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D017384:Sequence Deletion; D013329:Structure-Activity Relationship
chemical_list: D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D018960:Hyaluronan Receptors; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D006820:Hyaluronic Acid