TLR2
Synonyms
CD282, Toll-like receptor 2, TIL4, Toll/interleukin-1 receptor-like protein 4, TLR2, Toll Like Receptor 2, CD282 Antigen, EC:3.2.2.6
Description
Toll-like receptor 2 also known as TLR2 is a protein that in humans is encoded by the TLR2 gene. It cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components and cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides. It acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response, may also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins, and recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin (PSM) and B.burgdorferi outer surface protein A lipoprotein (OspA-L) cooperatively with TLR6. Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via this receptor, but also partially via TLR4. MAPK activation in response to bacterial peptidoglycan also occurs via this receptor. It acts as a receptor for M.tuberculosis lipoproteins LprA, LprG, LpqH and PstS1, some lipoproteins are dependent on other coreceptors (TLR1, CD14 and/or CD36); the lipoproteins act as agonists to modulate antigen presenting cell functions in response to the pathogen. M.tuberculosis HSP70 (dnaK) but not HSP65 (groEL-2) acts via this protein to stimulate NF-kappa-B expression and recognizes M.tuberculosis major T-antigen EsxA (ESAT-6) which inhibits downstream MYD88-dependent signaling (shown in mouse). Forms activation clusters composed of several receptors depending on the ligand, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway. It forms the cluster TLR2:TLR6:CD14:CD36 in response to diacylated lipopeptides and TLR2:TLR1:CD14 in response to triacylated lipopeptides and is required for normal uptake of M.tuberculosis, a process that is inhibited by M.tuberculosis LppM.
KO Status
F1 (+/-)
Drug Information
Launched drug: 1
Drugs in clinical trials: 5
Latest Research Phase: Approved
Drug Name
Code
Phase
Company
Indications
Clinical Trials
TR-987
Z-101, GLYC-101, MG-3601
Phase 2 Clinical
Kazia Therapeutics
Wounds and Injuries, Varicose Ulcer
Tomaralimab (Opsona Therapeutics)
OPN-305
Phase 2 Clinical
Opsona Therapeutics
Myelodysplastic Syndromes, Autoimmune Diseases, Delayed Graft Function, Inflammation
CBLB-612
CBLB-612
Phase 2 Clinical
Cleveland Biolabs
Hematopoietic stem cell transplantation (HSCT), Breast Neoplasms
DMT-210
DMT-200, DMT-210, DMT-220, SIG-990
Phase 2 Clinical
Signum Dermalogix
Rosacea, Dermatitis, Atopic
VB-201
CI-201, VB-201
Phase 2 Clinical
Vbl
Atherosclerosis, Coronavirus Disease 2019 (COVID-19), Psoriasis, Colitis, Ulcerative
DiaPep-277
DiaPep-277
Pending
Weizmann Institute Of Science
Diabetes Mellitus, Type 1
Macrophage-stimulating lipopeptide
Pending
Helmholtz Centre For Infection Research Gmbh
Wounds and Injuries
MALP-2S
MALP-2S
Discontinued
Mbiotec Gmbh
Pancreatic Neoplasms, Carcinoma, Non-Small-Cell Lung
Lyme disease vaccine (GlaxoSmithKline)
Withdrawn
Nonindustrial Source, Yale University
Lyme Disease
References
Title
Authors
Source
Host defense mechanisms triggered by microbial lipoproteins through Toll-like receptors
Brightbill H.D., Libraty D.H., Krutzik S.R., Yang R.B., Belisle J.T., Bleharski J.R., Maitland M., Norgard M.V., Plevy S.E., Smale S.T., Brennan P.J., Bloom B.R., Godowski P.J., Modlin R.L.,
Science 285:732-736(1999)
Cell activation and apoptosis by bacterial lipoproteins through Toll-like receptor-2
Aliprantis A.O., Yang R.-B., Mark M.R., Suggett S., Devaux B., Radolf J.D., Klimpel G.R., Godowski P.J., Zychlinsky A.,
Science 285:736-739(1999)
Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling
Bulut Y., Faure E., Thomas L., Equils O., Arditi M.,
J. Immunol. 167:987-994(2001)
A novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling
Yamamoto M., Sato S., Mori K., Hoshino K., Takeuchi O., Takeda K., Akira S.,
J. Immunol. 169:6668-6672(2002)
Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting
Triantafilou M., Gamper F.G., Haston R.M., Mouratis M.A., Morath S., Hartung T., Triantafilou K.,
J. Biol. Chem. 281:31002-31011(2006)
Four N-linked glycosylation sites in human toll-like receptor 2 cooperate to direct efficient biosynthesis and secretion
Weber A.N., Morse M.A., Gay N.J.,
J. Biol. Chem. 279:34589-34594(2004)
Mycobacterium tuberculosis heat shock proteins use diverse Toll-like receptor pathways to activate pro-inflammatory signals
Bulut Y., Michelsen K.S., Hayrapetian L., Naiki Y., Spallek R., Singh M., Arditi M.,
J. Biol. Chem. 280:20961-20967(2005)
The mycobacterial 38-kilodalton glycolipoprotein antigen activates the mitogen-activated protein kinase pathway and release of proinflammatory cytokines through Toll-like receptors 2 and 4 in human monocytes
Jung S.B., Yang C.S., Lee J.S., Shin A.R., Jung S.S., Son J.W., Harding C.V., Kim H.J., Park J.K., Paik T.H., Song C.H., Jo E.K.,
Infect. Immun. 74:2686-2696(2006)
TLR2 and its co-receptors determine responses of macrophages and dendritic cells to lipoproteins of Mycobacterium tuberculosis
Drage M.G., Pecora N.D., Hise A.G., Febbraio M., Silverstein R.L., Golenbock D.T., Boom W.H., Harding C.V.,
Cell. Immunol. 258:29-37(2009)
Non-acylated Mycobacterium bovis glycoprotein MPB83 binds to TLR1/2 and stimulates production of matrix metalloproteinase 9
Chambers M.A., Whelan A.O., Spallek R., Singh M., Coddeville B., Guerardel Y., Elass E.,
Biochem. Biophys. Res. Commun. 400:403-408(2010)