Requirements of src family kinase activity associated with CD45 for myeloma cell proliferation by interleukin-6.
Specific intracellular signals mediated by interleukin-6 (IL-6) receptor complexes, such as signal transducer and activator of transcription 3 (STAT 3) and extracellular signal-regulated kinase (ERK) 1/2, are considered to be responsible for inducing a variety of cellular responses. In multiple myeloma, IL-6 only enhanced the proliferation of CD45+ tumor cells that harbored the IL-6-independent activation of src family kinases even though STAT3 and ERK1/2 could be activated in response to IL-6 in both CD45+ and CD45(minus sign) cells. Furthermore, the IL-6-induced proliferation of CD45+ U266 myeloma cells was significantly suppressed by Lyn-specific antisense oligodeoxynucleotides or a selective src kinase inhibitor. These results indicate that the activation of both STAT3 and ERK1/2 is not enough for IL-6-induced proliferation of myeloma cell lines that require src family kinase activation independent of IL-6 stimulation. Thus, the activation of the src family kinases associated with CD45 expression is a prerequisite for the proliferation of myeloma cell lines by IL-6. We propose a mechanism for IL-6-induced cell proliferation that is strictly dependent upon the cellular context in myelomas.
Ishikawa
Hideaki
H
Department of Bio-Signal Analysis, Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.
Tsuyama
Naohiro
N
Abroun
Saeid
S
Liu
Shangqin
S
Li
Fu-Jun
FJ
Taniguchi
Osamu
O
Kawano
Michio M
MM
D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D017493:Leukocyte Common Antigens / Q000378:metabolism* / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009101:Multiple Myeloma / Q000473:pathology*; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000378:metabolism* / Q000502:physiology
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D017493:Leukocyte Common Antigens