Recombinant soluble interleukin-11 (IL-11) receptor alpha-chain can act as an IL-11 antagonist.
We have expressed a soluble N-glycosylated form of the murine interleukin-11 (IL-11) receptor alpha-chain (sIL-11R) and examined signaling in cells expressing the gp130 molecule. In the presence of gp130 but not the transmembrane IL-11R, the sIL-11R mediated IL-11-dependent differentiation of M1 leukemic cells and proliferation in Ba/F3 cells. Early intracellular events stimulated by the sIL-11R including phosphorylation of gp130, STAT 3, and SHP-2 were similar to signaling through the transmembrane IL-11R. IL-11 bound to sIL-11R with low affinity (kd 10 to 50 nmol/L). Binding of sIL-11R to gp130 was IL-11 dependent with intermediate affinity (kd 1.5 to 3.0 nmol/L). However, the concentration of IL-11 required for signaling through the sIL-11R was 10- to 20-fold greater than that required for cells expressing the transmembrane IL-11R and gp130 in the absence of sIL-11R. Furthermore, the sIL-11R was capable of antagonizing the activity of IL-11 when tested on cells expressing the transmembrane IL-11R and gp130. We propose that the observed IL-11 antagonism by the sIL-11R may depend on limiting numbers of gp130 molecules on cells already expressing the transmembrane IL-11R.
Curtis
D J
DJ
Walter and Eliza Hall Institute of Medical Research, Victoria, Australia.
Hilton
D J
DJ
Roberts
B
B
Murray
L
L
Nicola
N
N
Begley
C G
CG
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D016466:CHO Cells; D002455:Cell Division; D006224:Cricetinae; D050822:Cytokine Receptor gp130; D017370:Interleukin-11 / Q000037:antagonists & inhibitors*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D018123:Receptors, Interleukin / Q000378:metabolism*; D053702:Receptors, Interleukin-11; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D012995:Solubility
D015703:Antigens, CD; D017370:Interleukin-11; D008562:Membrane Glycoproteins; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11; D011994:Recombinant Proteins; D050822:Cytokine Receptor gp130