gp130 transducing receptor cross-linking is sufficient to induce interleukin-6 type responses.
gP130 transducing receptor is involved in the formation of high affinity receptors for the cytokines of the interleukin-6 (IL-6) family. Recruitment of gp130 by IL-6 associated to its receptor leads to the dimerization of the transducing component. In the present study we did characterize the B-S12 monoclonal antibody raised against gp130 and able to elicit IL-6 type biological activities. B-S12 antibody triggered strongly the proliferation of TF1 and XGI hematopoietic cell lines and was able to increase the synthesis of acute phase proteins in HepG2 hepatoma cell line. B-S12 also behaved as a synergistic factor with granulocyte-macrophage colony-stimulating factor for both proliferation and differentiation of CD34-positive hematopoietic cell progenitors. By using a symmetric enzyme-linked immunosorbent assay, allowing the detection of dimeric forms of soluble gp130, we found that addition of B-S12 to gp130 led to its dimerization. Analysis of the tyrosine phosphorylation events in gp130 and Jak kinase family members revealed that B-S12 quickly induced the phosphorylation of gp130 in a neural derived cell line, and that Jak1 and Jak2 were also recruited. In conclusion, we show that gp130 cross-linking with the B-S12 monoclonal antibody was sufficient to generate functional IL-6 type responses in hematopoietic, neural, and hepatic cells.
Fourcin
M
M
Laboratoire de Biologie Cellulaire, CHU Angers, France.
Chevalier
S
S
Guillet
C
C
Robledo
O
O
Froger
J
J
Pouplard-Barthelaix
A
A
Gascan
H
H
D015703:Antigens, CD / Q000737:chemistry / Q000502:physiology*; D018952:Antigens, CD34 / Q000032:analysis; D002454:Cell Differentiation; D002455:Cell Division; D050822:Cytokine Receptor gp130; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018952:Antigens, CD34; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D050822:Cytokine Receptor gp130; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2