Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors.
Members of the IL-6 cytokine family are involved in a variety of biological responses, including the immune response, inflammation, hematopoiesis, and oncogenesis by regulating cell growth, survival, and differentiation. These cytokines use gp130 as a common receptor subunit. The binding of ligand to gp130 activates the JAK/STAT signal transduction pathway, where STAT3 plays a central role in transmitting the signals from the membrane to the nucleus. STAT3 is essential for gp130-mediated cell survival and G1 to S cell-cycle-transition signals. Both c-myc and pim have been identified as target genes of STAT3 and together can compensate for STAT3 in cell survival and cell-cycle transition. STAT3 is also required for gp130-mediated maintenance of the pluripotential state of proliferating embryonic stem cells and for the gp130-induced macrophage differentiation of M1 cells. Furthermore, STAT3 regulates cell movement, such as leukocyte, epidermal cell, and keratinocyte migration. STAT3 also appears to regulate B cell differentiation into antibody-forming plasma cells. Since the IL-6/gp130/STAT3 signaling pathway is involved in both B cell growth and differentiation into plasma cells it is likely to play a central role in the generation of plasma cell neoplasias. Oncogene (2000).
Hirano
T
T
Division of Molecular Oncology C-7, Biomedical Research Center, Osaka University Graduate School of Medicine, 2-2 Yamada-oko, Suita, Osaka 565-0871, Japan.
Ishihara
K
K
Hibi
M
M
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement; D002470:Cell Survival; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D010954:Plasmacytoma / Q000378:metabolism / Q000473:pathology; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D050822:Cytokine Receptor gp130