Enhanced adhesion of monocytes via reverse signaling triggered by decoy receptor 3.
Decoy receptor 3 (DcR3), a newly identified soluble protein belonging to the tumor necrosis factor receptor (TNFR) superfamily, is a receptor for Fas ligand (FasL), LIGHT and TL1A. It has been demonstrated that DcR3 is frequently overexpressed by malignant tumors arising from lung, gastrointestinal tract, neuronal glia and virus-associated leukemia. Recently, we demonstrated that DcR3 is able to modulate the differentiation and activation of dendritic cells (DCs), and that DcR3-treated DCs skew naive T cell differentiation towards a Th2 phenotype. In this study, we further demonstrate that DcR3 is able to induce actin reorganization and enhance the adhesion of monocytes and THP-1 cells by activating multiple signaling molecules, such as protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), focal adhesion kinase (FAK) and Src kinases. This provides the first evidence that the soluble DcR3, like other immobilized members of TNFR superfamily, is able to trigger 'reverse signaling' to modulate cell function.
Hsu
Ming-Jen
MJ
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lin
Wan-Wan
WW
Tsao
Wei-Chia
WC
Chang
Yung-Chi
YC
Hsu
Tsui-Ling
TL
Chiu
Allen W
AW
Chio
Chung-Ching
CC
Hsieh
Shie-Liang
SL
D000199:Actins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000199:Actins; D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D008562:Membrane Glycoproteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D019061:src-Family Kinases; C505911:TNFRSF6B protein, human; C496050:PTK2 protein, human