A fusion protein of interleukin-11 and soluble interleukin-11 receptor acts as a superagonist on cells expressing gp130

Interleukin-11 is a hematopoietic cytokine that signals via the signal tran sducer gp130. Although gp130 is ubiquitously expressed, interleukine-11 res ponsiveness is restricted to cells that express the interleukine-11 recepto r alpha-subunit, The interleukine-11 receptor alpha-subunit can be function ally replaced by its soluble form indicating that the transmembrane and cyt oplasmic parts are not required for signal transduction. Here, we show that a recombinant fusion protein of a fragment of the human interleukine-11 re ceptor alpha-subunit ectodomain linked to human interleukine-11 acts as a s uperagonist on cells expressing gp130 but lacking the membrane-bound interl eukine-11 receptor alpha-subunit, It induces acute phase protein synthesis in hepatoma cells and efficiently promotes proliferation of Ba/F3 cells sta bly, transfected with gp130, In these bioassays, the fusion protein of a fr agment of the human interleukine-11 receptor alpha-subunit ectodomain linke d to human interleukine-11 is 50 times more potent than the combination of interleukine-11 and the soluble interleukine-11 receptor alpha-subunit, Thu s, our findings support the concept that covalent fusion of two soluble pro teins required for receptor activation dramatically increases their bioacti vity, (C) 1999 Federation of European Biochemical Societies.