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PDX1 activates insulin, somatostatin, glucokinase, islet amyloid polypeptide and glucose transporter type 2 gene transcription. IPF1 is particularly involved in glucose-dependent regulation of insulin gene transcription. Pancreas Duodenum Homeobox-1 binds preferentially the DNA motif 5'-[ct]taat[tg]-3'. During development, specifies the early pancreatic epithelium, permitting its proliferation, branching and subsequent differentiation. At adult stage, it is required for maintaining the hormone-producing phenotype of the beta-cell.

Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) was first characterized as a growth factor that supports the in-vitro colony formation of granulocytes-macrophages progenitor cells. It is a pleiotropic cytokine and a member of a family of endogenous cytokines of the hematopoietic system. GM-CSF is produced as a response to immune or inflammatory stimuli by activated cells of the hematopoietic system such as T cells, B cells, macrophages, mast cells and also fibroblasts and alveolar epithelial cells. It plays an important role in regulating the proliferation, differentiation, survival and activation of hematopoietic cells such as granulocytes and monocytes ,neutrophiles, basophiles and eosonophoiles, erythroid cells, megakaryocytes and T cells.
Human and mouse GM-CSF have about 56% homology and are species specific. Human GM-CSF is not active on mouse cells and vice versa. It is active on canine and feline cells.
GMCSF is 144 amino acids, 22kDa glycoprotein. It is composed of four bundles alpha helices. Its receptor is heterodimers with a ligand-specific alpha subunit and a betac subunit that is shared with the interleukin IL-3 and IL-5 receptors. This unusual form of receptor assembly likely applies also to IL-3 and IL-5 receptors. Cross-linking the two receptor subunits is required for receptor activation and signaling .
GMCSF has been shown to be involved in maturation, mobilization and antigen presentation of myeloid dentritic cells (DCs) in-vivo or ex-vivo. This function promotes Th1 immune responses, cytotoxcity, anti-angiogenesis as well as allergic inflammation, and the development of autoimmunity. Therefore GMCSF can be used in immunotherapy for the treatment of immune suppressed and immune-compromised patients as well as in veterinary medicine for the same purpose. GM-CSF is also important in regulation of embryo development and pregnancy and specifically in embryo implantation and subsequent development .

C3b is derived from native C3 upon cleavage with the alternative pathway C3 convertase and release of C3a. C3b is essential to the function of all 3complement pathways. Initiation of each pathway generates proteolytic enzyme complexes (C3 convertases) which binds the target surface. These enzymes cleave a peptide bond in C3 releasing the anaphylatoxin C3a and activating C3b. Most of the C3b created during complement activation. Surface-bound C3b is needed in all 3 pathways for effective activation of C5 and formation of C5b-9 complexes which lyse the target cell membrane. Surface-bound C3b and its breakdown products iC3b and C3d are identifyid by various receptors on lymphoid and phagocytic cells which use the C3b ligand to stimulate antigen presentation to cells of the adaptive immune system. It results in an expansion of target-specific B-cell and T-cell populations.

Epidermal growth factor has a profound effect on the differentiation of specific cells in vivo and is a potent mitogenic factor for a variety of cultured cells of both ectodermal and mesodermal origin. The EGF precursor is believed to exist as a membrane-bound molecule which is proteolytically cleaved to generate the 53-amino acid peptide hormone that stimulates cells to divide. EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture.

CIB1 (Calcium and integrin binding 1) is regulatory protein with 50% homology to calmodulin and calcineurin B, that encodes a member of the calcium-binding protein family. CIB1 interacts with DNA-dependent protein kinase and may play a role in kinase-phosphatase regulation of DNA end joining. Also CIB1 is widely expressed and binds to a number of effectors, such as integrin αIIb, PAK1, and polo-like kinases, in different tissues.

Clusterin also named Apolipoprotein J (APO-J) is a 75-80 kD disulfide-linked heterodimeric protein containing about 30% of N-linked carbohydrate rich in sialic acid but truncated forms targeted to the nucleus have also been identified. The precursor polypeptide chain is cleaved proteolytically to remove the 22-mer secretory signal peptide and subsequently between residues 227/228 to generate the ? and ? chains. These are assembled in anti-parallel to give a heterodimeric molecule in which the cysteine-rich centers are linked by five disulfide bridges and are flanked by two predicted coiled-coil ? -helices and three predicted amphipathic a-helices. Across a broad range of species clusterin shows a high degree of sequence homology ranging from 70% to 80%. It is nearly ubiquitously expressed in most mammalian tissues and can be found in plasma, milk, urine, cerebrospinal fluid and semen. It is able to bind and form complexes with numerous partners such as immunoglobulins, lipids, heparin, b

CD40 is part of the TNF-receptor superfamily. CD40 is a necessary mediator for vast range of immune and inflammatory responses together with T cell-dependent immunoglobulin class switching, memory B cell growth, and germinal center formation. The transcription factor AKNA regulates the expression of CD40 and its ligand, which is vital for homotypic cell interactions. Adaptor protein TNFR2 interacts with CD40 and serves as a mediator of the signal transduction. The interaction of CD40 and its ligand is crucial for amyloid-beta-induced microglial activation, and thus is thought to be an early event in Alzheimer disease pathogenesis. CD40 is the receptor for TNFSF5/CD40L.

Placental Lactogen is a polypeptide hormone that is produced by the Syncytiotrophoblasts of the Placenta, also known as chorionic somatomammotropin. It has both Growth Hormone and Prolactin activities on growth, lactation, and luteal steroid production. In women, placental lactogen secretion begins soon after implantation and increases to 1 g or more a day in late pregnancy. Placental lactogen is also an insulin antagonist.
Placental Lactogen Bovine is also capable of activating human and other heterologous GH receptors but not ruminat GH receptors.

Vimentin expression in human malignant glioma cells depends on cellular density, algorithms of drug delivery and chemo/radio treatment. Vimentin and detyrosinated microtubules provide structural support for the extensive microtentacles observed in detached tumor cells and a mechanism to promote successful metastatic spread. Primary colorectal carcinomas display aberrant expression of vimentin, and have activated Notch and TGFbeta signaling pathways. Vimentin is a strong arterial substrate for transglutaminases. Transglutaminase-mediated vimentin dimerization results in a novel unifying pathway by which vasodilatory and remodeling responses may be regulated. Ablation of vimentin expression inhibits migration and invasion of colon and breast cancer cell lines. Vimentin is the main intermediate filament protein in mesenchymal cells and is therefore of value in the differential diagnosis of undifferentiated neoplasms.

Basigin Isoform 2 or BSG is a part of the immunoglobulin superfamily, it is a type 1 transmembrane protein which has a variety of Nand O- glycosylation. BSG has several ligands, such as integrins, cyclophilin proteins Cyp-A & CyP-B. The protein has a crucial role in intercellular recognition, it takes part in many immunologic processes, differentiation and cell development. Also, it regulates numerus cell processes such as production and release of expression of the mono-carboxylate transporter, spermatogenesis, etc. Basigin Isoform 2 promotes invasion, metastasis, growth and survival of malignant cells by producing and releasing matrix metalloproteinases nearby mesenchymal cells and tumor cells.

GCSF is a cytokine that controls the production, differentiation, and function of granulocytes. The active protein is found extracellularly. 3 transcript variants encoding 3 different isoforms have been found for the GCSF gene. Granulocyte/macrophage colony-stimulating factors are cytokines that take part in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This csf induces granulocytes.

Connective Tissue Growth Factor belongs to the CCN family of proteins. The CCN family presently consists of six members in human also known as: Cyr61 (Cystein rich 61), CTGF (Connective Tissue Growth Factor), Nov (Nephroblastoma Overexpressed gene), WISP-1, 2 and 3 (Wnt-1 Induced Secreted Proteins). The CCN genes encode secreted proteins associated with the Extracellular Matrix (ECM) and cell membrane. CCN proteins are matricellular proteins which are involved in the regulation of various cellular functions including: proliferation, differentiation, survival, adhesion and migration. They are expressed in derivatives of the three embryonic sheets and are implicated in the development of kidney, nervous system, muscle, bone marrow, cartilage and bone. During adulthood, they are implicated in wound healing, bone fracture repair, and pathologies such as: fibrosis, vascular ailments and tumorigenesis.
Full length secreted CCN proteins can show an antiproliferative activity, whereas truncated isoforms are likely to stimulate proliferation and behave as oncogenes. The full length protein consists of four modulesModule I shares partial identity with the N-terminal part of the Insulin-like Growth Factor Binding Proteins (IGFBPs).
Module II includes a stretch of 70amino acid residues – which shares sequence identity with the Von Willebrand Factor Type C repeat (VWC).
Module III contains sequences sharing identity with the Thrombospondin type 1 repeat (TSP1) (WSXCSXXCG), which is thought to be implicated in the binding of sulfated glycoconjugates and to be important for cell adhesion. Module IV, also designated CT, is encoded by exon5. It is the leasts conserved one of the four domains at the level of nucleotide sequence, but it appears to be critical for several of the biological functions attributed to the CCN proteins. Module IV resembles the CT domain of several extracellular protein including, Von Willebrand's factor and mucins. Sequence similarities to heparin-binding motifs are also found within this domain. Proteolysis of the secreted full-length CCN proteins that has been reported in the case of CCN2 and CCN3 might result in the production of CCN-derived peptides with high affinity for ligands that full-length CNN proteins bind only poorly. Amino-truncated CCN2 isoforms were biologically active whereas no specific biological activity has been attributed to the truncated CCN3. Although the molecular processes underlying the production of these secreted isoforms is presently unknown, it is important to note that proteolysis occur at the same amino acid residues in both CCN2 and CCN3. An elevated expression of CCN2 has also been detected by Northern blotting in human invasive mammary ductal carcinomas, dermatofibromas, pyogenic granuloma, endothelial cells of angiolipomas and angioleiomyomas, and in pancreatic tumors. A study performed with chondrosarcomas representative of various histological grades established that CCN2 expression was closely correlated with increasing levels of malignancy. In agreement with CCN2 playing a role in brain tumor angiogenesis, immunocytochemistry studies indicated that both glioblastoma tumor cells and proliferating endothelial cells stained positive for CCN2. In astrocytomas, CCN2 expression was particularly elevated in high grade tumors, with a marked effect of CCN2 on cell proliferation. Downregulation of CCN2 expression in these cells was associated with a growth arrest at the G1/S transition while over-expression of CCN2 induced a two-fold increase of the number of cells in the G1 phase. Gene profiling analysis allowed to identify a set of about 50 genes whose expression might account for the proliferative activity of CCN2 in these cells.
CCN2 was seen in a higher proportion of mononuclear cells of patients with acute lymphoblastic leukemia.

Treponema pallidum is a gram-negative spirochaete bacterium and is considered to be metabolically crippled. There are at least four known subspecies: T. pallidum pallidum, T. pallidum pertenue, T. pallidum carateum and T. pallidum endemicum. The helical structure of T. pallidum pallidum allows it to move in a corkscrew motion through viscous mediums such as mucus. Treponema pallidum sub sp. pallidum has one of the smallest bacterial genomes at 1.14 million base pairs (Mb) and has limited metabolic capabilities, reflecting its adaptation through genome reduction to the rich environment of mammalian tissue.

Inhibins are dimeric peptide hormones produced by female ovarian granulose cells and male Sertoli cells as well as a variety of other tissues. Inhibins have two isoforms, A and B, with the same alpha subunit but different beta subunits. Inhibin A is a dimer of alpha and beta A subunits, inhibin B is a dimer of alpha and beta B subunits.
Inhibins are thought to inhibit the production of follicle-stimulating hormone (FSH) by the pituitary gland. In addition, Inhibins are also thought to play a role in the control of gametogenesis, and embryonic and fetal development.

GAPDH is a catalytic enzyme normally known to play a role in glycolysis. GAPDH exists as a tetramer composed of 36-kDa subunits and has a range of intracellular functions. GAPDH catalyzes the reversible reduction of 1,3-bisphosphoglycerate to glyceraldehyde 3-phosphophate in the presence of NADPH. Besides functioning as a glycolytic enzyme in cytoplasm, GAPDH has function in intracellular processes such as membrane fusion, microtubule bundling, phosphotransferase activity, nuclear RNA export, DNA replication and DNA repair. GAPDH catalyzes a vital energy-yielding step in carbohydrate metabolism, the reversible oxidative phosphorylation of glyceraldehyde-3-phosphate in the presence of inorganic phosphate and nicotinamide adenine dinucleotide (NAD). The enzyme exists as a tetramer of identical chains.

Chemokine (C-X-C motif) ligand (CXCL7) is a small cytokine belonging to the CXC chemokine family. It is a protein that is released in large amounts from platelets following their activation. It stimulates various processes including mitogenesis, synthesis of extracellular matrix, glucose metabolism and synthesis of plasminogen activator.

GCSF is a cytokine that controls the production, differentiation, and function of granulocytes. The active protein is found extracellularly. Three transcript variants encoding three different isoforms have been found for this gene.
Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This csf induces granulocytes.

The Fas receptor (CD95) mediates apoptotic signaling by Fas-ligand expressed on the surface of other cells. The Fas-FasL interaction plays an important role in the immune system and lack of this system leads to autoimmunity, indicating that Fas-mediated apoptosis removes self-reactive lymphocytes. Fas signaling is also involved in immune surveillance to remove transformed cells and virus infected cells. Binding of FAS to oligimerized FasL on another cell activates apoptotic signaling through a cytoplasmic domain termed the death domain that interacts with signaling adaptors including FAF, FADD and DAX to activate the caspase proteolytic cascade. Caspase-8 and caspase-10 are first activated, to then cleave and activate downstream caspases, and a variety of cellular substrates that lead to cell death. Caspases cleave nuclear lamins, causing the nucleus to break down and lose its normal structure and another caspase substrate is DFF, inducing cleavage and degradation of the genome. Other caspase substrates are involved in cytoskeletal structure, cell cycle regulation and signaling pathways. Activation of JNK kinase, activation of Jun, and production of ceramide may also play roles in Fas-mediated apoptosis. Activation of fas-mediated apoptosis is opposed by I-FLICE and FAP. Viruses and tumors may escape immune surveillance in part through suppression of fas-mediated apoptosis using similar mechanisms.

IFNI30 inducible lysosomal thiol reductase (IFI30), is a part of the GILT family. IFI30 is a lysosomal thiol reductase which at low pH is capable of decreasing protein’s disulfide bonds. IFI30 is expressed constitutively in antigen-presenting cells and induced by gamma-IFN in other cell types. Also, IFI30 plays an important role in MHC class II-restricted antigen processing. IFI30 facilitates the generation of MHC class II-restricted epitopes from disulfide bond-containing antigen by the endocytic reduction of disulfide bonds and Also facilitates MHC class I-restricted recognition of exogenous antigens containing disulfide bonds by CD8+ T-cells or cross-presentation.

S100A8 is a part of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a broad range of cells, and participate in the regulation of cellular processes such as cell cycle progression and differentiation. S100A8 plays a role in the inhibition of casein kinase and as a cytokine. S100A8 altered expression is related with cystic fibrosis disease. S100A8 is a calcium-binding protein that has antimicrobial activity against bacteria and fungi.S100A8 is crucial for resistance towards invasion by pathogenic bacteria. S100A8 up-regulates transcription of genes that are under the control of NF-kappa-B. S100A8 plays a role in the development of endotoxic shock in response to bacterial lipopolysaccharide. S100A8 endorses tubulin polymerization and promotes phagocyte migration and infiltration of granulocytes at sites of wounding. S100A8 takes part as a pro-inflammatory mediator in acute and chronic inflammation and up-regulates the release of IL8 and cell-surface expression of ICAM1.