A novel PKC-regulated mechanism controls CD44 ezrin association and directional cell motility.
The dynamic assembly and disassembly of membrane cytoskeleton junctional complexes is critical in cell migration. Here we describe a novel phosphorylation mechanism that regulates the hyaluronan receptor CD44. In resting cells, CD44 is constitutively phosphorylated at a single serine residue, Ser325. After protein kinase C is activated, a switch in phosphorylation results in CD44 being phosphorylated solely at an alternative residue, Ser291. Using fluorescence resonance energy transfer (FRET) monitored by fluorescence lifetime imaging microscopy (FLIM) and chemotaxis assays we show that phosphorylation of Ser291 modulates the interaction between CD44 and the cytoskeletal linker protein ezrin in vivo, and that this phosphorylation is critical for CD44-dependent directional cell motility.
Legg
James W
JW
Department of Biological Sciences, Imperial College of Science, Technology and Medicine, Sir Alexander Fleming Building, Imperial College Road, London SW7 2AZ, UK.
Lewis
Charlotte A
CA
Parsons
Maddy
M
Ng
Tony
T
Isacke
Clare M
CM
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D002465:Cell Movement / Q000502:physiology*; D003598:Cytoskeletal Proteins; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism*; D008545:Melanoma; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010703:Phorbol Esters / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000099149:Ezrin
D000911:Antibodies, Monoclonal; D003598:Cytoskeletal Proteins; D018960:Hyaluronan Receptors; D010703:Phorbol Esters; D010750:Phosphoproteins; D011493:Protein Kinase C; D012694:Serine; D000099149:Ezrin