TLR2

Synonyms

EC:3.2.2.6, CD282 Antigen, CD282, Toll-like receptor 2, TIL4, Toll/interleukin-1 receptor-like protein 4, TLR2, Toll Like Receptor 2

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

RenMab: Immunization

Drug Information

Drugs in clinical trials: 5
Latest Research Phase: Phase 2 Clinical

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Tomaralimab (Opsona Therapeutics)

OPN-305

Phase 2 Clinical

Opsona Therapeutics

Autoimmune Diseases, Myelodysplastic Syndromes, Delayed Graft Function, Inflammation

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

TR-987

Z-101, GLYC-101, MG-3601

Phase 2 Clinical

Kazia Therapeutics

Wounds and Injuries, Varicose Ulcer

CBLB-612

CBLB-612

Phase 2 Clinical

Cleveland Biolabs

Hematopoietic stem cell transplantation (HSCT), Breast Neoplasms

INNA-051

INNA-051

Preclinical

Coronavirus Disease 2019 (COVID-19)

VNLG-152

VNLG-152, HT-003

Preclinical

University Of Maryland, Baltimore

Acne Vulgaris, Neoplasms, Psoriasis

Macrophage-stimulating lipopeptide

Pending

Helmholtz Centre For Infection Research Gmbh

Wounds and Injuries

DiaPep-277

DiaPep-277

Pending

Weizmann Institute Of Science

Diabetes Mellitus, Type 1

MALP-2S

MALP-2S

Discontinued

Mbiotec Gmbh

Pancreatic Neoplasms, Carcinoma, Non-Small-Cell Lung

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)