IL-2 (mouse) (monomeric):Fc-KIH (human) (rec.) Reference: AG-40B-0225 Interleukin-2 (IL-2) is a 133 amino acid glycoprotein with one intramolecular disulfide bond and variable glycosylation. It is secreted by activated T cells and induces proliferation and maturation of activated T cells, natural killer cells and lymphokine activated killer cells. IL-2 also stimulates proliferation of antibody-producing B cells, activates neutrophils and induces mononuclear cells to secrete IFN-gamma and TNF-alpha and -beta. Moreover, studies have shown that IL-2 is required for activation-induced apoptosis, an important homeostatic mechanism in the immune system, which is involved in the maintenance of peripheral tolerance to self-antigens.IL-2 promotes T cell proliferation and particularly naive T cells. IL-2 signaling on activated T cells is effected through a quaternary high-affinity receptor complex consisting of IL-2, IL-2Ralpha (CD25), IL-2Rbeta and IL-2Rgamma. Naive T cells are relatively insensitive to IL-2 as they only express small amounts of IL-2Rbeta and IL-2Rgamma. They only acquire sensitivity after CD25 expression, which captures the cytokine and presents it to the IL-2Rbeta and IL-2Rgamma receptors. IL-2 is used in the treatment of metastatic cancer cells. Recently synergy has been observed between IL-2 based therapy and checkpoint blockade for cancer treatments. Cells which bear receptors for IL-2 stimulation are modulated by checkpoint inhibition either directly or through other lymphocytes, and lymphocytes which are effectors of checkpoint inhibition may respond to IL-2. The protein IL-2 (mouse) (monomeric):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-2 (mouse):Fc Knobs sequence (synthesizing a protein of 45kDa) and one encoding for the Fc Holes sequence (synthesizing a protein of 28kDa). Both vectors transfected into HEK293 cells produce both Fc molecules (Knobs-into-Holes technology; J.B. Ridgway, et al.; Protein Eng. 9, 617 (1996)) required for dimerization of the Fc moieties and for secretion of the final protein IL-2 (mouse) (monomeric):Fc-KIH (human) (rec.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.
IL-38 (aa 20-152) (human) (monomeric):Fc-KIH (human) (rec.) Reference: AG-40B-0226 IL-38 (IL-1F10) belongs to the IL-1 family of proteins. IL-38 is expressed in heart, placenta, fetal liver, spleen, thymus and tonsil. The expression in a variety of immune tissues and similarity to IL-1Ra suggest a role of IL-38 in the inflammatory response. It has been reported that removal of the N-terminus domain of the interleukins of the IL-1F family such as IL-1F5 / 6 / 8 or 9 (also called IL-36Ra, IL-36alpha, IL-36beta or IL-36gamma) is important to increase their biological activity. Recently it has been shown that IL-38 is N-terminally processed and secreted by apoptotic cells. Released processed IL-38 (20-152) binds to the receptor Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1; TIGIRR-2) at the surface of macrophages. Processed IL-38-activated IL1RAPL1 reduces the production of IL-6 leading to inflammation attenuation. IL-38 is unregulated during some autoimmune diseases such as Systemic Lupus Erythematosus. The protein IL-38 (human) (monomeric):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-38 (human):Fc Knobs sequence (synthesizing a protein of 45kDa) and one encoding for the Fc Holes sequence (synthesizing a protein of 28kDa). Both vectors transfected into HEK293 cells produce both Fc molecules (Knobs-into-Holes technology; J.B. Ridgway, et al.; Protein Eng. 9, 617 (1996)) required for dimerization of the Fc moieties and for secretion of the final protein IL-38 (human)(monomeric):Fc-KIH (human) (rec.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.
IL-38 (aa 3-152) (mouse) (monomeric):Fc-KIH (human) (rec.) Reference: AG-40B-0227 IL-38 (IL-1F10) belongs to the IL-1 family of proteins. IL-38 is expressed in heart, placenta, fetal liver, spleen, thymus and tonsil. The expression in a variety of immune tissues and similarity to IL-1Ra suggest a role of IL-38 in the inflammatory response. It has been reported that removal of the N-terminus domain of the interleukins of the IL-1F family such as IL-1F5 / 6 / 8 or 9 (also called IL-36Ra, IL-36alpha, IL-36beta or IL-36gamma) is important to increase their biological activity. Recently it has been shown that IL-38 is N-terminally processed and secreted by apoptotic cells. Released processed IL-38 (20-152) binds to the receptor Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1; TIGIRR-2) at the surface of macrophages. Processed IL-38-activated IL1RAPL1 reduces the production of IL-6 leading to inflammation attenuation. IL-38 is unregulated during some autoimmune diseases such as Systemic Lupus Erythematosus. The protein IL-38 (mouse) (monomeric):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-38 (mouse):Fc Knobs sequence (synthesizing a protein of 45kDa) and one encoding for the Fc Holes sequence (synthesizing a protein of 28kDa). Both vectors transfected into HEK293 cells produce both Fc molecules (Knobs-into-Holes technology; J.B. Ridgway, et al.; Protein Eng. 9, 617 (1996)) required for dimerization of the Fc moieties and for secretion of the final protein IL-38 (mouse) (monomeric):Fc-KIH (human) (rec.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.
PLpro (SARS-CoV-2) (rec.) (His) Reference: SBB-DE0127 The severe acute respiratory syndrome coronavirus papain-like protease (SARS-CoV PLpro) is involved in the processing of the viral polyprotein. Proteolytic processing of the coronavirus replicase poly-protein is essential for generating a functional virus replication complex. PLpro possesses both deubiquitinating or deISGylating activity and can process Lys48 and Lys63 linked polyubiquitin chains (free chains or from cellular substrates). It works in concert together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. It strongly antagonizes the innate immune induction of type I interferon by blocking the phosphorylation, dimerization and therefore the nuclear translocation of host IRF3. In addition, it prevents also host NF-kappa-B signaling. SARS Cov-2 PLpro is very active hydrolyzing both ISG15-Rhodamine110 (SBB-PS0002) or di-ubiquitin/tetra-ubiquitin substrates (Lys48 or Lys63 linked), but is very inefficient when processing mono-Ub conjugates e.g. Ub-AMC or synthetic peptide substrates e.g. RLRGG-AMC. This SARS Coronavirus recombinant PLpro is N-terminally His10-tagged and expressed in E.coli.
Mpro [3CLpro] (SARS-CoV-2) (rec.) (His) Reference: SBB-DE0129 3CLpro recognizes the peptide sequence LQ[S/A/G] where it cleaves c-terminal to the amino acid glutamine (use product SBB-PS0130, KTSAVLQ-Rh110-Glu as universal substrate). The protease 3CLpro is a potential drug target for coronavirus infections due to its essential role in processing the polyproteins that are translated from the viral RNA. The X-ray structures of the unliganded SARS-CoV-2 protease 3CLpro and its complex with an alpha-ketoamide inhibitor provides a basis for design of alpha-ketoamide inhibitors. This SARS Coronavirus recombinant 3CLpro is N-terminally His10-tagged and expressed in E.coli.
TRF-Ubiquitin Mix (100X) (400 reactions) Reference: SBB-TR0051-4H Ubiquitin is a highly conserved protein that plays a major role in the ubiquitination pathway, which is conserved from yeast to mammals. Ubiquitination, the conjugation of ubiquitin to other proteins through a covalent bond between its C-terminal glycine and the epsilon-amino group of lysine residues or the alpha-amino group of an N- terminal methionine onto proteins is essential for many cellular processes primarily linked to protein degradation. This process involves three steps with specific groups of enzymes in an ATP depended manner, which are activation with ubiquitin-activating enzymes (E1s), conjugation with ubiquitin-conjugating enzymes (E2s) and ligation with ubiquitin ligases (E3s).
CD152 [CTLA-4] (human) (rec.) (His) Reference: AG-40B-0228 CD152 (Cytotoxic T-lymphocyte-associated protein 4; CTLA-4) is an inhibitory receptor belonging to the CD28 immunoglobulin subfamily, expressed primarily by T-cells. Its ligands, CD80 and CD86, are typically found on the surface of antigen-presenting cells and can either bind CD28 or CTLA-4, resulting in a costimulatory or a co-inhibitory response, respectively. Because of its dampening effect, CTLA-4 is a crucial regulator of T-cell homeostasis and self-tolerance. While CD28 promotes T-cell activation and proliferation, CTLA-4 is reported to dampen T-cell responses through a variety of mechanisms. Prior to activation, conventional T-cells (Tconv) express low levels of CTLA-4, predominantly in intracellular compartments. Upon activation, CTLA-4 expression is upregulated and becomes increasingly detectable on the cell surface. In Tregs on the other hand, transmembrane CTLA-4 is constitutively expressed and plays an important role in Treg homeostasis and function. In general, T-cell CTLA-4 is largely constrained to intracellular expression although some surface expression may be detectable owing to the rapid, continuous shuttling of CTLA-4 between intracellular compartments and the plasma membrane. Recently, roles of CTLA-4 have been demonstrated in dendritic cells and tumors, showing that CTLA-4 plays nonredundant and critical roles in thymic development, T-cell priming, peripheral tolerance, and a variety of other critical immunoregulatory functions as an immune checkpoint in Immuno-oncology research.
Sortilin (human) (rec.) (His) Reference: AG-40B-0229 Sortilin is a type I transmembrane multiligand receptor that is a member of the Vacuolar protein sorting 10 protein (Vps10p) domain receptor family. It is a 95 kDa protein, ubiquitously expressed, although most abundantly expressed in neurons, hepatocytes, adipocytes and white blood cells including macrophages. Sortilin is synthesized as a propeptide in the endoplasmic reticulum (ER) and processed to its mature form by furin-mediated cleavage in the trans-Golgi network. The primary function of sortilin is trafficking proteins from the Golgi to secretory vesicles and endolysosomal compartments. The majority of trafficking is from the Golgi to the endosomal compartment where sortilin deposits cargo targeted for catabolism in the lysosome and then is trafficked back to the Golgi via a retromer complex. At the cell surface, sortilin can remain intact and act as a receptor for extracellular ligands that can initiate signaling cascades or be internalized as a method of receptor-mediated endocytosis. Additionally, cell surface sortilin protein can undergo an additional cleavage that results in the release of the soluble form of the protein into the extracellular space. The sortilin receptor binds the nerve growth factor precursor (proNGF), neurotensin and Progranulin (PGRN), a secreted growth factor implicated in a multitude of processes ranging from regulation of inflammation to wound healing, tumorigenesis and neurological diseases. Sortilin controls PGRN trafficking and lysosomal degradation, but PGRN exerts its multiple functions independent of sortilin. Sortilin down-regulation via blocking antibodies is a key mechanism in increasing PGRN levels suggesting that sortilin is a potential target to correct PGRN reduction, such as that in patients with frontotemporal dementia (FTD) caused by GRN mutations.
IL-22 (human):Fc (human) (rec.) (non-lytic) Reference: AG-40B-0230 The IL-22 gene includes five exons and a 537 bp-long open reading frame that encodes for a 179 amino acid protein. IL-22 is a member of the IL-10 family of cytokines, which also includes IL-19, -20, -24, and -26, IL-28A/B, and IL-29 and IFNlambda. Mouse and human IL-22 share 79% homology. IL-22 is mainly produced by lymphocytes, such as T helper type 1 (Th1), Th17, Th22, CD8+ T cells, gammadelta T cells, natural killer cells, lymphoid tissue inducer cells, innate lymphoid type 3 (ILC3) cells, and also by neutrophils. IL-22 has two heterodimeric transmembrane receptors, IL-22R1 and IL-10R2, which subsequently activate the JAK/STAT3, ERK and JNK pathways. IL-22 responsiveness is limited by epithelial cell-restricted expression of IL-22RA1 in the lung, gastrointestinal tract, thymus, skin, pancreas, liver, and kidney and represents a major communication channel between the immune system and specialized tissue cell types. IL-22 is a critical regulator of epithelial homeostasis, implicated in multiple aspects of epithelial barrier function, including regulation of epithelial cell growth and permeability, production of mucus and antimicrobial proteins (AMPs) and complement production. IL-22 plays key functions in the intestine and, therefore, plays a protective role in inflammatory bowel disease (IBD). IL-22 is also a controversial cytokine in tumor development; the IL-22-STAT3 axis induces anti-apoptotic genes and provides survival and proliferation signals for both normal and malignant cells. Therefore, in healthy conditions, it prevents tumor formation; however, once a tumor has been established, IL-22 promotes tumorigenesis.
CD24 (human)-muIg Fusion Protein Reference: ANC-559-020 CD24 is a highly glycosylated protein expressed as glycosyl-phosphatidyl-inositol (GPI) anchored molecule. It is widely expressed, mainly on T cells, B cells and is upregulated in numerous types of cancers. It has costimulatory activity for antigen specific T cell responses. Polymorphisms of human CD24 are associated with several autoimmune diseases. Recently, a new role as negative regulator of the immune response has been reported. CD24-deficient mice are more sensitive to inflammatory responses. CD24 together with the membrane protein SIGLEC interacts with danger-associated molecular patterns (DAMPs), such as HMGB1, HSP90 or HSP70. CD24/SIGLEC complex may differentially regulate the host response to DAMPs and PAMPs (pathogen-associated molecular patterns).
CD24 (human)-muIg Fusion Protein (preservative free) Reference: ANC-559-820 CD24 is a highly glycosylated protein expressed as glycosyl-phosphatidyl-inositol (GPI) anchored molecule. It is widely expressed, mainly on T cells, B cells and is upregulated in numerous types of cancers. It has costimulatory activity for antigen specific T cell responses. Polymorphisms of human CD24 are associated with several autoimmune diseases. Recently, a new role as negative regulator of the immune response has been reported. CD24-deficient mice are more sensitive to inflammatory responses. CD24 together with the membrane protein SIGLEC interacts with danger-associated molecular patterns (DAMPs), such as HMGB1, HSP90 or HSP70. CD24/SIGLEC complex may differentially regulate the host response to DAMPs and PAMPs (pathogen-associated molecular patterns).
Fc (human) IgG1 Control (rec.) (non-lytic) Reference: AG-35B-0016 Negative control in experiments with recombinant proteins fused to Fc (human) IgG1 (non-lytic) (e.g. Prod. No. AG-40B-0230). This protein is not an appropriate negative control for other standard Fc protein constructs. Mutations to the complement (C1q) and FcgR I binding sites of the IgGs Fc fragment render the non-lytic proteins incapable of antibody-directed cytotoxicity (ADCC) and complement-directed cytotoxicity (CDC).