A rapid translocation of CD45RO but not CD45RA to lipid rafts in IL-6-induced proliferation in myeloma

Blood. 2005 Apr 15;105(8):3295-302. doi: 10.1182/blood-2004-10-4083. Epub 2004 Dec 30.


CD45, a receptor-type tyrosine phosphatase, is required for interleukin-6 (IL-6)-induced proliferation in human myeloma cells, which express the shortest isoform, CD45RO, but not the longest isoform, CD45RA. Here, we showed that IL-6 induced the translocation of CD45 to lipid rafts in an isoform-dependent manner. In myeloma cells, CD45RO was translocated to lipid rafts more rapidly than CD45RB, but exogenously expressed CD45RA was not translocated. When an IL-6Ralpha-transfected B-cell line was stimulated with IL-6, CD45RA was not translocated, although CD45RB was. We further confirmed that the translocated CD45 bound to IL-6Ralpha, Lyn, and flotillin-2, and this was followed by the dephosphorylation of the negative regulatory Tyr507 of Lyn. CD45 also bound to phosphoprotein associated with glycosphingolipid-enriched microdomains (PAGs), which were subsequently dephosphorylated, resulting in the release of C-terminal src kinase (Csk) from lipid rafts. Therefore, these results indicate that a rapid translocation of CD45RO to lipid rafts may be responsible for IL-6-induced proliferation, and that the change from CD45RA to CD45RO confers the ability to respond to IL-6 in human myeloma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Green Fluorescent Proteins / genetics
  • Humans
  • Interleukin-6 / pharmacology*
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / metabolism*
  • Membrane Microdomains / metabolism*
  • Membrane Proteins / metabolism
  • Multiple Myeloma
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Transport / drug effects
  • Protein Transport / physiology
  • Receptors, Interleukin-6 / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Tyrosine / metabolism
  • src-Family Kinases / metabolism


  • Adaptor Proteins, Signal Transducing
  • Interleukin-6
  • Membrane Proteins
  • PAG1 protein, human
  • Phosphoproteins
  • Receptors, Interleukin-6
  • Recombinant Proteins
  • flotillins
  • Green Fluorescent Proteins
  • Tyrosine
  • lyn protein-tyrosine kinase
  • src-Family Kinases
  • Leukocyte Common Antigens