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

F0

Drug Information

Launched drugs: 5
Drug in clinical trials: 1
Latest Research Phase:Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Lyme disease vaccine (GlaxoSmithKline)

Approved

Nonindustrial Source, Yale University

Lyme Disease

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

VB-201

CI-201, VB-201

Phase 2 Clinical

Vbl

Atherosclerosis, Psoriasis, Colitis, Ulcerative

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

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