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A fusion protein of interleukin‐11 and soluble interleukin‐11 receptor acts as a superagonist on cells expressing gp130
Author(s) -
Pflanz Stefan,
Tacken Ingrid,
Grötzinger Joachim,
Jacques Yannick,
Dahmen Heike,
Heinrich Peter C.,
Müller-Newen Gerhard
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00477-9
Subject(s) - ectodomain , glycoprotein 130 , fusion protein , microbiology and biotechnology , receptor , interleukin 5 receptor alpha subunit , biology , protein subunit , interleukin 10 receptor, alpha subunit , chemistry , signal transduction , g alpha subunit , recombinant dna , biochemistry , stat3 , gene
Interleukin‐11 is a hematopoietic cytokine that signals via the signal transducer gp130. Although gp130 is ubiquitously expressed, interleukine‐11 responsiveness is restricted to cells that express the interleukine‐11 receptor α‐subunit. The interleukine‐11 receptor α‐subunit can be functionally replaced by its soluble form indicating that the transmembrane and cytoplasmic parts are not required for signal transduction. Here, we show that a recombinant fusion protein of a fragment of the human interleukine‐11 receptor α‐subunit ectodomain linked to human interleukine‐11 acts as a superagonist on cells expressing gp130 but lacking the membrane‐bound interleukine‐11 receptor α‐subunit. It induces acute phase protein synthesis in hepatoma cells and efficiently promotes proliferation of Ba/F3 cells stably, transfected with gp130. In these bioassays, the fusion protein of a fragment of the human interleukine‐11 receptor α‐subunit ectodomain linked to human interleukine‐11 is 50 times more potent than the combination of interleukine‐11 and the soluble interleukine‐11 receptor α‐subunit. Thus, our findings support the concept that covalent fusion of two soluble proteins required for receptor activation dramatically increases their bioactivity.