Search results

Interleukin-5 receptor subunit alpha (Il5ra) regulates the development and function of eosinophils. The Il5ra protein is a therapeutic target for hypereosinophilic diseases including allergic inflammations and asthma. Oct2 enhances antibody-secreting cell differentiation via regulation of Il5ra chain expression on activated B cells.

Interleukin-6 Signal Transducer or IL6ST is a receptor, part of the family of class 1 cytokine receptor. IL6ST binds to IL-6 through membrane-anchored or soluble IL-6R starts a connection between another complex of IL6ST and IL-6 , thus forming a homo-dimer and a signal transduction occurs.

BCA-1 is a CXC chemokine that is highly expressed in thesecondary lymphoid organs, such as follicles of the spleen, lymph nodes, and Peyer's patches. CXCL13 promotes the migration of B lymphocytes (compared to T cells and macrophages), by stimulating calcium influx into, and chemotaxis of, cells expressing Burkitt's lymphoma receptor 1 (BLR1). BCA1 therefore function in the homing of B lymphocytes to follicles. Human BCA-1 shares a 64% amino acid sequence similarity with the mouse protein and 23 - 34% amino acid sequence identity with other known CXC chemokines. Recombinant or chemically synthesized BCA1 is a potent chemoattractant for B lymphocytes but not T lymphocytes, monocytes or neutrophils. BLR1, a G protein-coupled receptor originally isolated from Burkitt’s lymphoma cells, has now been shown to be the specific receptor for BCA1. Among cells of the hematopoietic lineages, the expression of BLR-1, now designated CXCR-5, is restricted to B lymphocytes and a subpopulation of T helper memory cells.

BCAT1 catalyzes the leading reaction in the catabolism of the indispensable branched chain amino acids isoleucine, leucine and valine.

IL17 is a proinflammatory cytokine produced by activated T cells. IL-17 regulates the activities of NF-kappaB and mitogen-activated protein kinases. Interleukin-17 can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhance the production of nitric oxide (NO). High levels of IL-17 are associated with several chronic inflammatory diseases including rheumatoid arthritis, psoriasis and multiple sclerosis.

Human CCL16, also called HCC-4, liver-expressed chemokine (LEC), and lymphocyte and monocyte chemoattractant (LMC), is a novel CC chemokine recognized by bioinformatics. NCC-4 cDNA encodes a 120 amino acids along with a 23 amino acids signal peptide that is cleaved to generate 97 amino acid protein. HCC4 is vaguely related to other CC chemokines, showing less than 30% sequence identity. Among CC chemokines, CCL-16 has the largest similarity to HCC-1. 2 potential polyadenylation signals are present on the human HCC-4 gene, and as a result, 2 transcripts containing roughly 1,500 base pairs and 500 base pairs have been detected. HCC-4 is expressed weakly by some lymphocytes, including NK cells, T cells, and some T cell clones. The expression of HCC-4 in monocytes is greatly upregulated in the presence of IL-10.
CCL16 shows chemotactic activity for lymphocytes and monocytes rather than to neutrophils. NCC-4 has potent myelosuppressive activity, suppresses proliferation of myeloid progenitor cells. CCL16 demonstrates chemotactic activity for monocytes and thp-1 monocytes, rather than for resting lymphocytes and neutrophils. HCC-4 induces a calcium flux in thp-1 cells that desensitized prior to the expression of rantes.

PPP1R14A is a phosphorylation-dependent inhibitor of smooth muscle myosin phosphatase. Inhibition of PPP1R14A results to increased myosin phosphorylation and enhances smooth muscle contraction in the absence of increased intracellular Ca(2+) concentration. Myosin phosphatase can reverse MYL (myosin light chain) phosphorylation to induce a state of relaxation. However, during agonist-induced contraction at constant Ca2+ concurrent inhibition of myosin phosphatase leads to increases in MYL phosphorylation and tension. These calcium-independent increases in myosin phosphorylation and tension are termed calcium sensitization. Human pregnancy is characterized by the increases of PKN1 expression and CPI-17 phosphorylation in the myometrium. PPP1R14A is mapped to chromosome 19q13.13-q13.2. PPP1R14A binds directly to protein kinase C and casein kinase I. PPP1R14A siRNA decreased the level of merlin phosphorylation and consequently Ras and ERK activity in human tumor cell lines. PKC/CPI-17 medi

Influenza A virus subtype H5N1 is a subtype of the Influenza A virus. Subtype H5N1 is commonly known as avian influenza or bird flu. H5N1 may cause more than one influenza pandemicas it is expected to continue mutating in birds. The dominant strain of HPAI A (H5N1) evolved creating the Z genotype. It has also been called Asian lineage HPAI/A/H5N1 which is divided into 2 antigenic clades. "Clade 1 includes human and bird isolates from Vietnam, Thailand, and Cambodia and bird isolates from Laosand Malaysia. Clade 2 viruses were first identified in bird isolates from China, Indonesia, Japan, and South Korea before spreading westward to the Middle East, Europe, and Africa.

Junctional Adhesion Molecule 2 (JAM2) is a member of the immunoglobulin superfamily, and the junctional adhesion molecule (JAM) family. JAM2 is a type I membrane protein which is localized at the tight junctions of both epithelial and endothelial cells. JAM2 functions as an adhesive ligand for interacting with various immune cell types, and may have a role in lymphocyte homing to secondary lymphoid organs.

SARS Coronavirus is an enveloped virus containing three outer structural proteins, namely the membrane (M), envelope (E), and spike (S) proteins. Spike (S)-glycoprotein of the virus interacts with a cellular receptor and mediates membrane fusion to allow viral entry into susceptible target cells. Accordingly, S-protein plays an important role in virus infection cycle and is the primary target of neutralizing antibodies.It has recently been shown that SARS is caused by a human coronavirus. Human coronaviruses are the major cause of upper respiratory tract illness in humans, such as the common cold. Coronaviruses are positive-stranded RNA viruses, featuring the largest viral RNA genomes known to date (27-31 kb). The first step in coronavirus infection is binding of the viral spike protein, a 139-kDa protein, to certain receptors on host cells. The spike protein is the main surface antigen of the coronavirus. The most prominent protein in the culture supernatants infected with SARS virus is a 46 kDa nucleocapsid protein. This suggests that the nucleocapsid protein is a major immunogen that may be useful for early diagnostics.

ABI gene family member 3 (ABI3) is a member of the ABI family. Members of the ABI family encode proteins which contain a homeobox homology domain, proline rich region and Src-homology 3 (SH3) domain. Abi family members are assumed to negatively regulate cell growth and transformation, including cellular transformation through v-Abl as well controlling as mediate cell motility by regulating actin polymerization in lamellipodia and filopodia. ABI3 impedes ectopic metastasis of tumor cells as well as cell migration, which is accomplished through interaction with p21-activated kinase.

Transforming growth factor betas (TGFBetas) mediate many cell-cell interactions that occur during embryonic development. Three TGFBetas have been identified in mammals. TGFBeta1, TGFBeta2 and TGFBeta3 are each synthesized as precursor proteins that are very similar in that each is cleaved to yield a 112 amino acid polypeptide that remains associated with the latent portion of the molecule. This antibody reacts with the precursor and mature form of TGFBeta2 and to a lesser extent TGFBeta3, but does not cross react with TGFBeta1.

DACT3 which belongs to the DACT (Dpr/Frodo) gene family plays an imperative role in a negative regulator of Wnt/-catenin signaling. Unlike other Wnt signaling inhibitors that are silenced by DNA methylation, DACT3 repression is linked to bivalent histone modifications.

CACYBP (calcyclin binding protein) participates in calcium-dependent ubiquitination and subsequent proteosomal degradation of target proteins. CACYBP acts as a molecular bridge in ubiquitin E3 complexes. CACYBP is involved in the ubiquitin-mediated degradation of beta-catenin.

BCL2 gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Two transcript variants, produced by alternate splicing, differ in their C-terminal ends.

ASB13 belongs to the ankyrin repeat and SOCS box-containing (ASB) family of proteins which contains ankyrin repeat sequence and a SOCS box domain. ASB13 is a protein coding gene that plays a role as a substrate-recognition part of a SCF-like ECS E3 ubiquitin-protein ligase complex which arbitrates the ubiquitination and subsequent proteasomal degradation of target proteins.

The epidermal growth factor receptor (EGF R) subfamily of receptor tyrosine kinases comprises four members: EGF R (also known as HER1, ErbB1 or ErbB), ErbB2 (Neu, HER-2), ErbB3 (HER-3), and ErbB4 (HER-4). All family members are type I transmembrane glycoprotein that has an extracellular domain which contains two cysteine-rich domains separated by a spacer region that is involved in ligand-binding, and a cytoplasmic domain which has a membrane-proximal tyrosine kinase domain and a C-terminal tail with multiple tyrosine autophosphorylation sites. The human EGF R gene encodes a 1210 amino acid (aa) residue precursor with a 24 aa putative signal peptide, a 621 aa extracellular domain, a 23 aa transmembrane domain, and a 542 aa cytoplasmic domain. EGF R has been shown to bind a subset of the EGF family ligands, including EGF, amphiregulin, TGF-a , betacellulin, epiregulin, heparin-binding EGF and neuregulin-2 in the absence of a co-receptor. Ligand binding induces EGF R homodimerization as well as heterdimerization with ErbB2, resulting in kinase activation, tyrosine phosphorylation and cell signaling. EGF R can also be recruited to form heterodimers with the ligand-activated ErbB3 or ErbB4. EGF R signaling has been shown to regulate multiple biological functions including cell proliferation, differentiation, motility and apoptosis. In addition, EGF R signaling has also been shown to play a role in carcinogenesis.

ASF1A is part of the H3/H4 family of histone chaperone proteins corresponding to the anti-silencing function-1 gene in yeast. ASF1A is an important element of the histone donor complex that functions in nucleosome assembly. ASF1A interacts with histones H3 and H4, and functions together with a chromatin assembly factor during DNA replication and repair. Deletion of ASF1A in yeast and Drosophila confers sensitivity to various DNA damaging agents and inhibitors of DNA replication, increases genomic instability and sister chromatid exchange, and activates the DNA damage checkpoint.

Listeriolysin O (aka LLO) is a hemolysin produced by Listeria monocytogenes bacteria, the pathogen responsible for causing listeriosis. The toxin may be regarded as a virulence factor, since it is crucial for the virulence of L. monocytogenes. LLO is a single polypeptide protein encoded by the hlyA gene and composed of 529 residues. LLO is a thiol-activated cholesterol-dependent pore forming toxin protein; therefore, it is activated by reducing agents and inhibited by oxidizing agents. Still, LLO differs from other thiol-activated toxins, as its cytolytic activity is maximized at a pH of 5.5. Inside the acidic phagosomes (average pH ~ 5.9) of cells that have phagocytosed L. monocytogenes, LLO is selectively activated by maximizing activity at a pH of 5.5. Following the phagosome lysis by LLO, the bacterium breaks out into the cytosol, where it is able to grow intracellularly, and the toxin has reduced activity in the more basic cytosol. Thus, LLO permits L. monocytogenes to break out from the phagosomes into the cytosol without harming the plasma membrane of the infected cell, which allows the bacteria to live intracellularly, where they are sheltered from extracellular immune system factors such as the complement system and antibodies. LLO also brings about dephosphorylation of histone H3 and deacetylation of histone H4 in the early phases of infection, before entry of L. monocytogenes into the host cell. The pore-forming activity is not implicated in causing the histone modifications. The modifications of the histones affect the down regulation of genes encoding proteins involved in the inflammatory response. Therefore, LLO may be significant in subverting the host immune response to L. monocytogenes. At its NH2-terminus it possesses a 25 residues long typical signal sequence excited during the secretion process. Moreover, in its NH2-terminus there is also a 19 amino acids PEST- like sequence that may target this toxin for degradation. The PEST-like sequence found in LLO and is considered crucial for virulence, given that mutants lacking the sequence lysed the host cell. Nevertheless, contrary to PEST's supposed role in protein degradation, evidence implies that the PEST-like sequence may control LLO production in the cytosol rather than increase degradation of LLO.

RAB5A is a member of RAS oncogene family. The small GTPase, RAB5A is a crucial regulatory component of the endocytic pathway. Activation of RAB5A is mediated by GDP-GTP exchange factors (GEFs) that generate the Rab5-GTP complex). RAB5A is required for the fusion of plasma membranes and early endosomes.

IFN regulatory factor 2 is a member of the IFN regulatory transcription factor (IRF) family. IRF2 competitively inhibits the IRF1-mediated transcriptional activation of IFNs alpha and beta, and presumably other genes that employ IRF1 for transcription activation. However, IRF2 also functions as a transcriptional activator of histone H4. IRF2 binds to the upstream regulatory region of type-1 IFN and IFN-inducible MHC class-1 genes (the IFN consensus sequence (ics) and represses those genes.

IL36RA belongs to the IL-1 family of proteins. IL36RA is produced as a 156 aa protein which holds no signal sequence, no prosegment and no potential N-linked glycosylation site but, IL36RA is secreted as a 17 kDa monomer. Cells known to express IL36Ra/IL1F5 include monocytes, B cells, keratinocytes, dendritic cells/Langerhans cells and gastric fundus Parietal and Chief cells.

Inhibitor of Growth Family, Member 2 (ING2) belongs to the inhibitor of growth (ING) family. ING family members associate with and modulate the activity of histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes and serve in DNA repair and apoptosis. ING2 appears to be involved in p53/TP53 activation and p53/TP53-dependent apoptotic pathways, most likely by enhancing acetylation of p53/TP53. ING2 is a component of an mSin3A-like corepressor complex, which is probably involved in deacetylation of nucleosomal histones. ING2 activity is modulated by binding to phosphoinositides (PtdInsPs).

CD40L or CD154 is a membrane glycoprotein and differentiation antigen expressed on the surface of T-cells. The CD40 ligand stimulates B-cell proliferation and secretion of all immunoglobulin isotypes in the presence of cytokines. CD40 ligand has been shown to induce cytokine production and tumoricidal activity in peripheral blood monocytes. It also costimulates proliferation of activated T-cells and this is accompanied by the production of IFN-gamma , TNF-alpha , and IL2.