A rapid translocation of CD45RO but not CD45RA to lipid rafts in IL-6-induced proliferation in myeloma.
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.
Li
Fu-Jun
FJ
Department of Bio-Signal Analysis, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.
Tsuyama
Naohiro
N
Ishikawa
Hideaki
H
Obata
Masanori
M
Abroun
Saeid
S
Liu
Shangqin
S
Otsuyama
Ken-ichiro
K
Zheng
Xu
X
Ma
Zi
Z
Maki
Yasuko
Y
Kawano
Michio M
MM
D048868:Adaptor Proteins, Signal Transducing; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009101:Multiple Myeloma; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015850:Interleukin-6; D008565:Membrane Proteins; C498710:PAG1 protein, human; D010750:Phosphoproteins; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; C106354:flotillins; D049452:Green Fluorescent Proteins; D014443:Tyrosine; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D017493:Leukocyte Common Antigens