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, Thes e cytokines use gp130 as a common receptor subunit, The binding of ligand t o gp130 activates the JAK/STAT signal transduction pathway, where STAT3 pla ys a central role in transmitting the signals from the membrane to the nucl eus. STAT3 is essential for gp130-mediated cell survival and G1 to S cell-c ycle-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 c ell-cycle transition. STAT3 is also required for gp130-mediated maintenance of the pluripotential state of proliferating embryonic stem cells and for the gp130induced macrophage differentiation of Mt cells. Furthermore, STAT3 regulates cell movement, such as leukocyte, epidermal cell, and keratinocy te migration. STAT3 also appears to regulate B cell differentiation into an tibody-forming plasma cells. Since the IL-6/gp130/STAT3 signaling pathway i s involved in both B cell growth and differentiation into plasma cells it i s likely to play a central role in the generation of plasma cell neoplasias .