latency

Transforming Growth Factor β-1 (TGFβ-1) is a secreted protein which belongs to the TGF-β family. TGFβ-1 is abundantly expressed in bone, articular cartilage and chondrocytes and is increased in osteoarthritis (OA). TGFβ-1 performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiation and apoptosis. The precursor is cleaved into a latency-associated peptide (LAP) and a mature TGFβ-1 peptide. TGFβ-1 may also form heterodimers with other TGFβ family members. It has been found that TGFβ-1 is frequently upregulated in tumor cells. Mutations in this gene results in Camurati-Engelmann disease.

Transforming growth factor beta 1 (TGFβ1) is the prototype of a growing superfamily of peptide growth factors and plays a prominent role in a variety of cellular processes, including cell-cycle progression, cell differentiation, reproductive function, development, motility, adhesion, neuronal growth, bone morphogenesis, wound healing, and immune surveillance. TGF-β1, TGF-β2 and TGF-β3 signal via the same heteromeric receptor complex, consisting of a ligand binding TGF-β receptor type II (TβR-II), and a TGF-β receptor type I (TβR-I). Signal transduction from the receptor to the nucleus is mediated via SMADs. TGF-β expression is found in cartilage, bone, teeth, muscle, heart, blood vessels, haematopoitic cells, lung, kidney, gut, liver, eye, ear, skin, and the nervous system.

Transforming growth factor beta 3(TGFB3) is a member of a TGF -β superfamily which is defined by theirstructural and functional similarities. TGFB3 is secreted as a complex with LAP. This latent form of TGFB3becomes active upon cleavage by plasmin, matrix metalloproteases, thrombospondin -1, and a subset ofintegrins. It binds with high affinity to TGF- β RII, a type II serine/threonine kinase receptor. TGFB3 is involved incell differentiation, embryogenesis and development.It is believed to regulate molecules involved in cellularadhesion and extracellular matrix (ECM) formation during the process of palate development. Without TGF-β3,mammals develop a deformity known as a cleft palate.

Integrin alpha V beta 8 is a receptor for fibronectin. It recognizes the sequence R-G-D in its ligands. ITGAVB8 does not appear to assume different activation states; and the cytoplasmic tail does not connect to the cytoskeleton. It binds ligands containing an RGD motif; including vitronectin; fibrin and the latency associated peptide (LAP) of the latent TGF-beta complex. High affinity binding of alpha V beta 8 to LAP allows proteolytic cleavage by MT1-MMP; which releases active TGF-beta. This mechanism differs from that of alpha V beta 6; the other alpha V integrin which can activate TGF-beta from latency through non-proteolytic mechanisms.

Integrin alpha-V:beta-8 (ITGAV:ITGB8) is a receptor for fibronectin. It recognizes the sequence R-G-D in its ligands. Integrin alpha-V:beta-6 (ITGAV:ITGB6) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation on the surface of activated regulatory T-cells (Tregs). Required during vasculogenesis. ITGB8 Protein, Rabbit, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 31.9 kDa and the accession number is P26013.

Thrombospondin-1 (TSP-1) is a 150-180kDa calcium-sensitive protein that is secreted as a disulfide-linked homotrimer. TSP-1 regulates a wide range of cellular functions including their interactions with other cells and with the extracellular matrix (ECM). TSP-1 contains an N-terminal Laminin G-like globular domain, an extended central region with one vWFC domain, 3 TSP type 1domains, 2 EGF-like domains, and 8 TSP type3 domains, and a globular TSP C-terminal domain. Distinct regions of TSP-1 have been associated with binding to particular ECM or cellular molecules. TSP-1 counteracts the angiogenic, hypotensive, and antithrombotic effects of nitric oxide (NO). It binds and neutralizes VEGF, blocks VEGF R2 signaling on vascular endothelial cells(EC), and destabilizes adhesive contacts between EC. TSP-1 also plays an important role in wound repair and tissue fibrosis by binding latent TGF-beta and inducing release of the active cytokine from the latency associated peptide (LAP).

Transforming growth factor beta (TGFβ) family members are secreted in inactive complexes with a latency-associated peptide (LAP), a protein derived from the N-terminal region of the TGFβ gene product. Extracellular activation of these complexes is a critical step in regulation of TGFβ function in vivo. The TGFβ1 LAP is a ligand for the integrin αvβ6 and that αvβ6-expressing cells induce spatially restricted activition of TGFβ1. And LAP identifies a novel CD4+/CD25+ regulatory T cell subset with TGFbeta-mediated function and enhanced suppression of experimental autoimmune encephalomyelitis.

Leucine Rich Repeat Containing 32 (LRRC32), also known as Glycoprotein A Repetitions Predominant (GARP), has been postulated as a novel surface marker of activated T(regs). LRRC32 binds directly to the TGF-beta latency associated peptide (LAP) and tethers latent TGF-beta on the surface of activated Treg cells. The presentation of TGF-beta on Tregs contributes to their ability to suppress naïve T cell proliferation. LRRC32 is widely expressed during embryogenesis and on adult platelets. Human LRRC32 is identified as a lineage specific key receptor for human T cells.

Immediate-early transcription factor that controls the initiation of viral lytic gene expression and lytic reactivation from latency. Triggers lytic replication, and initiates a cellular senescence program in epithelial cells. Upregulates human DCR3/TNFRSF6B by directly binding to its receptor. Epstein-Barr virus (strain GD1) BRLF1 Protein (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 34.9 kDa and the accession number is Q3KSS7.

Key regulator of transforming growth factor beta-1 (TGFB1) specifically required for microglia function in the nervous system. Required for activation of latent TGF-beta-1 in macrophages and microglia: associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGFB1, and regulates integrin-dependent activation of TGF-beta-1. TGF-beta-1 activation mediated by LRRC33/NRROS is highly localized: there is little spreading of TGF-beta-1 activated from one microglial cell to neighboring microglia, suggesting the existence of localized and selective activation of TGF-beta-1 by LRRC33/NRROS. Indirectly plays a role in Toll-like receptor (TLR) signaling: ability to inhibit TLR-mediated NF-kappa-B activation and cytokine production is probably a consequence of its role in TGF-beta-1 signaling (Probable).