Requirements of src family kinase activity associated with CD45 for myeloma cell proliferation by interleukin-6.

Abstract

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.

• Authors: Hideaki Ishikawa, Naohiro Tsuyama, Saeid Abroun, Shangqin Liu, Fu-Jun Li, Osamu Taniguchi, Michio M Kawano
• Journal: Blood (Blood) Vol. 99 Issue 6 Pg. 2172-8 (Mar 15 2002) ISSN: 0006-4971 [Print] United States
• PMID: 11877294 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Interleukin-6
• STAT3 Transcription Factor
• STAT3 protein, human
• Trans-Activators
• lyn protein-tyrosine kinase
• src-Family Kinases
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases
• Leukocyte Common Antigens

Topics

• Cell Division (drug effects)
• DNA-Binding Proteins (metabolism)
• Enzyme Activation (drug effects, physiology)
• Humans
• Interleukin-6 (pharmacology)
• Leukocyte Common Antigens (metabolism, physiology)
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases (metabolism)
• Multiple Myeloma (pathology)
• STAT3 Transcription Factor
• Trans-Activators (metabolism)
• Tumor Cells, Cultured
• src-Family Kinases (metabolism, physiology)