FIGURE 1 

A comprehensive molecular interaction map of TLR signaling network. The SBML and PDF files of the map are available from the Supplementary information. The map can be best viewed in the PDF format. All of the species, proteins, and reactions included in the map are listed in the SBML file when opened by CellDesigner (http://celldesigner.org/). Abbreviations: A20, tumor necrosis factor-inducible protein A20; Akt, v-akt murine thymoma viral oncogene homolog; ASK, apoptosis signal-regulating kinase; ATF, activating transcription factor; Bcl, B-cell CLL/lymphoma; beta-TrCP, beta-transducin repeat-containing protein; BTK, Bruton agammaglobulinemia tyrosine kinase; CaM, calmodulin; CaMKI, calcium/calmodulin-dependent protein kinase; CBP, CREB-binding protein; c-Cbl, Casitas B-lineage lymphoma proto-oncogene; CD, cluster of differentiation; Cdc42, cell division cycle 42 (GTP-binding protein, 25 kDa); CK, casein kinase; c-Myc, v-myc myelocytomatosis viral oncogene homolog; CRE, cAMP response element; CREB, cAMP response element-binding protein; CsgA, major curlin subunit precursor, Salmonella enterica; c-Src, v-src sarcoma (Schmidt–Ruppin A-2) viral oncogene homolog (avian); C-TAK1, MAP/microtubule affinity-regulating kinase 3; CYLD, cylindromatosis (turban tumor syndrome); DAG, diacylglycerol; dsRNA, double-strand RNA; ECSIT, evolutionarily conserved signaling intermediate in toll pathway; EEA, early endosome antigen; eIF, eukaryotic translation initiation factor; Elk-1, ETS domain protein Elk-1; ERK, extracellular signal-regulated kinase; FADD, Fas-associated via death domain; Fos, v-fos FBJ murine osteosarcoma viral oncogene homolog; gp91phox, glycoprotein of 91 kDa from phagocyte oxidase; GSK, glycogen synthase kinase; HDAC, histone deacetylase, HMG, high-mobility group nucleosome-binding domain; hnRNP, heterogeneous nuclear ribonucleoprotein; HSP, heat-shock protein; Ibtk, inhibitor of Bruton agammaglobulinemia tyrosine kinase; ICE, interleukin 1-B-converting enzyme; IB, nuclear factor of light polypeptide gene enhancer in B-cells inhibitor; IKK, I--B kinase; IL, interleukin; IL-1ra, interleukin 1 receptor antagonist; IL-1RAcP, interleukin 1 receptor accessory protein; IP3, inositol 1,4,5-triphosphate; IP3R, inositol 1,4,5-triphosphate receptor; IRAK, interleukin 1 receptor-associated kinase; IRF, interferon-regulatory factor; ISRE, interferon-a-stimulated response element; JNK, c-Jun N-terminal kinase; Jun, v-jun sarcoma virus 17 oncogene homolog (avian); KSR, kinase suppressor of ras; LBP, lipopolysaccharide-binding protein; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; MAPKAPK, mitogen-activated protein kinase-activated protein kinase; MBP, myelin basic protein; MD-2, lymphocyte antigen 96; MEKK, MAPK/ERK kinase kinase; MKK, mitogen-activated protein kinase kinase; MKP, MAP kinase phosphatase; MMT virus, mouse mammary tumor virus; Mnk, MAP kinase interacting serine/threonine kinase; MSK, mitogen- and stress-activated protein kinase; MyD88, myeloid differentiation primary response gene 88; NF-B, nuclear factor B; NIK, nuclear factor B-inducing kinase; NOD, nucleotide-binding oligomerization domain; NSF, N-ethylmaleimide-sensitive factor; NUR77, nuclear receptor subfamily 4, group A, member 1; p62, phosphotyrosine-independent ligand for the Lck SH2 domain p62; PAK, p21-activated kinase; PDK, 3-phosphoinositide-dependent protein kinase; pellino, pellino (Drosophila) homolog; PI(4)P5K, phosphatidylinositol-5-kinase; PI, phosphatidylinositol; Pi, phosphoric ion; PI3,4,5-P3, phosphatidylinositol-3,4,5-triphosphate; PI3,4-P2, phosphatidylinositol-3,4-bisphosphate; PI3K, phosphatidylinositol-3-kinase; PI3-P, phosphatidylinositol-3-phosphate; PI4,5-P2, phosphatidylinositol-4,5-bisphosphate; PI4-P, phosphatidylinositol-4-phosphate; PKA, protein kinase A; PKC, protein kinase C; PKR, eukaryotic translation initiation factor 2- kinase; PLC, phospholipase C; PLD, phospholipase D; PP, protein phosphatase; Rab, RAS-associated protein; Rabaptin, RAB GTPase-binding effector protein; Rabex, RAB guanine nucleotide exchange factor; Rac, ras-related C3 botulinum toxin substrate; Raf, v-raf-1 murine leukemia viral oncogene homolog; Ras, rat sarcoma viral oncogene homolog; Rho, ras homolog gene family; RhoGDI, GDP dissociation inhibitor; Rin, Ras interaction; RIP, receptor-interacting serine–threonine kinase; RKIP, Raf kinase inhibitor protein; RS virus, respiratory syncytial virus; Sab, SH3-domain-binding protein 5 (BTK-associated); SERCA, sarcoplasmic/endoplasmic reticulum calcium ATPase; SIGIRR, single immunoglobulin and toll-interleukin 1 receptor (TIR) domain; SOCS, suppressor of cytokine signaling; ssRNA, single-strand RNA; ST2L, interleukin 1 receptor-like 1; STF, soluble tuberculosis factor; TAB, transforming growth factor beta-activated kinase-binding protein; TAK, transforming growth factor beta-activated kinase; TBK, TRAF family member-associated nuclear factor B activator-binding kinase; TICAM, toll-like receptor adaptor molecule; TIFA, TRAF-interacting protein with a forkhead-associated domain; TIR, toll-interleukin 1 receptor; TIRAP, toll-interleukin 1 receptor domain-containing adaptor protein; TLR, toll-like receptor; TOLLIP, toll-interacting protein; TPL, tumor progression locus; TRAF, tumor necrosis factor receptor-associated factor; TRAILR, tumor necrosis factor-related apoptosis-inducing ligand receptor; TRIAD3A, ubiquitin-conjugating enzyme 7-interacting protein 1, isoform A; TRIP, thyroid hormone receptor interactor; Trx, thioredoxin; Ubc, ubiquitin-conjugating enzyme; Uev, ubiquitin-conjugating enzyme E2 variant; Vav1, vav 1 oncogene.