A schematic model of the IL-6 receptor system. Both IL-6Rα and gp130 belong to the type I cytokine receptor family. Many hematopoietic cells express both IL-6Rα and gp130 as shown to the left, and the complex can bind IL-6 and signal through gp130 with signal transduction through JAK1, JAK2, or TYK2 (shown here as JAK) and STATs -1, -3 and –5 (STAT). As shown on the right, hematopoietic stem cells may lack the IL-6Rα and thus may be unable to bind IL-6 to form a signaling complex through gp130. The soluble extracellular domain of the IL6Rα can bind IL-6, forming a complex that can bind to gp130, activating signal transduction in stem cells.