Trans-signaling of interleukin-6 (IL-6) is mediated by the soluble IL-6 receptor, but not by soluble CD5.
IL-6 exerts its pleiotropic activities on its target cells via the IL-6 alpha-receptor (IL-6R), which is expressed on a limited number of cell types. IL-6 can further signal via soluble forms of its receptor (sIL-6R), a process that has been termed trans-signaling. Recently, CD5 was described as an alternative alpha-receptor for IL-6 on B cells leading to the phosphorylation of the transcription factor STAT3 via the signal-transducing β-receptor gp130 in a Jak2-dependent manner. In this study, we sought to investigate whether IL-6 was also able to signal via soluble CD5 (sCD5) analogous to IL-6 trans-signaling. We show that IL-6 indeed binds to sCD5, but that this does not lead to the activation of signal transduction or cell proliferation. Furthermore, sCD5 did also not interfere with IL-6 classic signaling, suggesting that the affinity between the two proteins was too weak to provoke a biological effect. Thus, trans-signaling of IL-6 can only occur via sIL-6R, but not sCD5.
Institute of Biochemistry, Kiel University, 24118 Kiel, Germany.
Samadhi
S
Aparicio-Siegmund
Institute of Biochemistry, Kiel University, 24118 Kiel, Germany.
Malte
M
Deseke
Institute of Biochemistry, Kiel University, 24118 Kiel, Germany.
Annett
A
Lickert
Institute of Biochemistry, Kiel University, 24118 Kiel, Germany. Electronic address: cgarbers@biochem.uni-kiel.de.
Christoph
C
Garbers
D001665:Binding Sites; D018956:CD5 Antigens / Q000737:chemistry* / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D019947:Receptors, Interleukin-6 / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D012995:Solubility
D018956:CD5 Antigens; D015850:Interleukin-6; D019947:Receptors, Interleukin-6
CD5; Interleukin-6; STAT3; Trans-signaling