TLRs: differential adapter utilization by toll-like receptors mediates TLR-specific patterns of gene expression.
In response to microbial or environmental "danger" signals, represented by structural motifs not normally expressed by cells, Toll-like receptors mediate intracellular signaling that leads to inflammatory gene expression. In response to agonists, TLR aggregation enables the recruitment and/or activation of TLR-specific adapter molecules. To date, four adapter proteins have been identified: MyD88, TIRAP/Mal, TRIF/TICAM-1, and TIRP/TRAM/TICAM-2. The interaction of the different TLRs with distinct combinations of adapter molecules creates a platform to which additional kinases, transacting factors, and possibly other molecules are recruited, events that lead, ultimately, to gene expression. Given the rapidity with which such interactions have been described, we have attempted to summarize our current understanding of the adapters that are so essential for TLR signaling and provide a working model for future studies.
Departments of Microbiology and Immunology and Medicine, University of Maryland, Baltimore, MD, USA. svogel@som.umaryland.edu
Stefanie N
SN
Vogel
Katherine A
KA
Fitzgerald
Matthew J
MJ
Fenton
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000943:Antigens, Differentiation / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000235:genetics; D015398:Signal Transduction; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000943:Antigens, Differentiation; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; C470409:TICAM1 protein, human; C480228:TICAM2 protein, human; C434984:TIRAP protein, human; D051193:Toll-Like Receptors