Cross talk between MyD88 and focal adhesion kinase pathways.
Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase involved in signaling downstream of integrins, linking bacterial detection, cell entry, and initiation of proinflammatory response through MAPKs and NF-kappaB activation. In this study, using protein I/II from Streptococcus mutans as a model activator of FAK, we investigated the potential link between FAK and TLR pathways. Using macrophages from TLR- or MyD88-deficient mice, we report that MyD88 plays a major role in FAK-dependent protein I/II-induced cytokine release. However, response to protein I/II stimulation was independent of TLR4, TLR2, and TLR6. The data suggest that there is a cross talk between FAK and MyD88 signaling pathways. Moreover, MyD88-dependent, LPS-induced IL-6 secretion by human and murine fibroblasts required the presence of FAK, confirming that MyD88 and FAK pathways are interlinked.
Zeisel
Mirjam B
MB
Institut National de la Santé et de la Recherche Médicale 392, Faculté de Pharmacie, Illkirch, France.
Druet
Vanessa A
VA
Sibilia
Jean
J
Klein
Jean-Paul
JP
Quesniaux
Valérie
V
Wachsmann
Dominique
D
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology*; D001426:Bacterial Proteins / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D009569:Nitric Oxide / Q000096:biosynthesis; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D020239:Receptor Cross-Talk / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000502:physiology; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D013295:Streptococcus mutans / Q000276:immunology; D013583:Synovial Membrane / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D001426:Bacterial Proteins; D039081:Integrin alpha5beta1; D015850:Interleukin-6; D008024:Ligands; D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C055764:S-layer proteins; C495368:TLR6 protein, human; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C495369:Tlr6 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse