Recombinant TB-38kD Protein

Functions in inorganic phosphate uptake, although probably not the main uptake protein under phosphate starvation. Binds phosphate; probably able to bind both H2PO4-and HPO42-. Part of the ABC transporter complex PstSACB involved in phosphate import. A host TLR2 agonist (toll-like receptor), shown experimentally for human and mouse. Requires both host TLR1 and TLR2 as coreceptors to elicit host response in mouse (TLR6 may also play a role) neither CD14 or CD36 function as accessory receptors. Protein purified from culture filtrate induces host (human) monocytes to produce TNF-alpha, IL-6 and IL-12 p40 (IL12B) via ERK1/2 (MAPK3 and MAPK1) and p38 MAPK pathways; MEK inhibitors U0126 and PD98059 and p38 inhibitor SB203580 block most cytokine production. Host ERK1/2 and p38 MAPK activation is mediated mainly by TLR2, but also partially by TLR4, and unlike the case for lipoprotein LpqH the protein moiety of PstS1 seems to be the antigenic agent. Greater activation of ERK1/2 and p38 MAPK is seen in patients with active pulmonary tuberculosis than in tuberculin-negative patients. Induces apoptosis when incubated with human monocyte-derived macrophages via TLR2. Protein purified from culture filtrate acts via TLR2 and TLR4 to induce host macrophage (shown for mouse) endoplasmic reticulum stress-mediated apoptosis via MAPK (at least JNK), C-C motif chemokine 2 (MCP-1, Ccl2) and ZC3H12 endoribonucleases (MCPIP, Zc3h12). Functions as an adhesin, binds to human and mouse macrophages via mannose residues, binds to the mouse macrophage mannose receptor (possibly Mrc1) and mediates bacterial phagocytosis.