Smad3 and STAT3 are intracellular molecules that transmit signals from plasma membrane receptors to the nucleus. Smad3 operates downstream of growth/differentiation factors that utilize activin receptor-like kinase (ALK)-4, 5, or 7, such as transforming growth factor-β (TGF-β), activin, and myostatin. STAT3 principally functions downstream of cytokines that exert their effects via gp130 and Janus family kinases, including interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and oncostatin M. Accumulating evidence indicates that Smad3 and STAT3 engage in crosstalk in a highly context-dependent fashion, cooperating in some conditions while acting antagonistically each other in others. Here, we review the crosstalk between Smad3 and STAT3 in various biological contexts, including early tumorigenesis, epithelial-mesenchymal transition, fibrosis, and T cell differentiation.
Keywords: STAT; Smad; TGF-β; crosstalk.
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