Search results

HB-EGF is an EGF related growth factor which signals via the EGF receptor, and stimulates the proliferation of SMC (smooth muscle cells), fibroblasts, epithelial cells and keratinocytes. HB-EGF is expressed in various cell types and tissues, including vascular endothelial cells and SMC, macrophages, skeletal muscle, keratinocytes and particular tumor cells. HB-EGF’s ability to explicitly bind HPR sulfate proteoglycans is dissimilar from other EGF-like molecules, and might be related to the enhanced mitogenic activity, relative to EGF, that HB-EGF exerts on smooth muscle cells.

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.

Mycobacterium antigen ESAT6 has been isolated from low molecular weight fractions of the shot-term-culture filtrate (ST-CF) and it can easily be detected in tuberculosis patients. The export of ESAT-6 which is a potent T-cell antigen, and related proteins requires a dedicated secretory apparatus that is encoded by a group of genes, several of which also code for proteins that are recognized strongly by T cells. The ESAT-6 systems can consequently be considered as immunogenicity islands and there is mounting evidence that the equivalent genes are subject to selective pressure imposed by the immune system of the host. This antigen includes many epitopes detectable in the serum of most patients with tuberculosis (more than 90%). By the attempts to obtain the vaccine on the basis of ESAT-6 it was demonstrated that the optimization of adjuvant is very important when using the combination of dioctadecylammonium bromide and monophosphoryllipide. ESAT-6 is very potential as diagnostic for differentiation between the mycobacterial infection and BCG vaccination. The main topic in ESAT-6 using is in antibody production and in test-systems for tuberculosis elaboration. Early secretory antigen 6 (ESAT6) and cell filtrate protein 10 (CFP10) are 2 antigens secreted as a complex by the replicating Mycobacterium tuberculosis complex (MTC).

TGFB2 is a 27.08 kDa protein having two identical 118 amino acid peptide chains linked by a single disulfide bond. TGFB2 is part of a family of five related cytokines that have an extensive variation of normal and neoplastic cells, indicating the importance of these homo-dimmer proteins as multi-functional regulators of cellular activity. The three mammalian isoforms of TGF-β (TGFb1, TGFb2 and TGFb3) signal through the same receptor and stimulate similar biological responses. They are involved in physiological processes as embryogenesis, tissue remodelling and wound healing.

TGFB2 is a 27.08 kDa protein having two identical 118 amino acid peptide chains linked by a single disulfide bond. TGFB2 is part of a family of five related cytokines that have an extensive variation of normal and neoplastic cells, indicating the importance of these homo-dimmer proteins as multi-functional regulators of cellular activity. The three mammalian isoforms of TGF-beta (TGFb1, TGFb2 and TGFb3) signal through the same receptor and stimulate similar biological responses. They are involved in physiological processes as embryogenesis, tissue remodelling and wound healing.

NELFE is a vital component of NELF complex which represses RNA polymerase II transcript elongation. NELFE is similar to nuclear RNA-binding proteins but does not bind RNA. NELFE contains a tract of alternating basic and acidic residues, mainly arginine and aspartic acid.

Glutamyl-TRNA Amidotransferase, Subunit C also known as GATC allows the formation of properly charged Gln-tRNA(Gln) through the transamidation of misacylated Glu-tRNA(Gln) in the mitochondria. The reaction occurs in the attendance of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln). In addition, GATC is subunit of the heterotrimeric GatCAB amidotransferase (AdT) complex, composed of A (QRSL1), B (PET112) and C (GATC) subunits.

SUMF1 is a part of the SUMF protein family. SUMF1 catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue called C-alpha-formylglycine. Mutations in this gene will cause multiple sulfatase deficiency meaning a lysosomal storage disorder.

Pre-mRNA-splicing factor SYF2 (SYF2) may be involved in pre-mRNA splicing. The SYF2 protein interacts with cyclin D-type binding-protein 1, which is believed to be a cell cycle regulator at the G1/S transition. SYF2 is amply expressed in the heart, skeletal muscle and kidney and is expressed at lower levels in other tissues.

Complement factor H (CFH) is an important regulatory component of the alternative pathway of complement. CFH is prevents complement activation on host cells and tissues, mainly the kidney. CFH controls the formation and decay of the alternative pathway C3/C5 convertase and acts as a cofactor for factor I which proteolytically inactivates C3b when C3b is bound to factor H. The N-terminal 5 domains of CFH bind to C3b and inhibit binding of factor B thus reducing the formation of C3/C5 convertase. CFH also binds to preformed C3/C5 convertases and causes quick release of the catalytic subunit Bb. These activities are necessary for controlling the spontaneous activation of the alternative pathway amplification process in plasma. In addition, CFH controls the formation and decay of these enzymes when C3b is attached to the surface of particles.

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.

Based on sequence similarity to VEGF-A, a gene encoding a VEGF homologue has recently been discovered in the genome of Orf virus (OV) (Lyttle et al., 1994). Different isolates of Orf virus show significant amino acid sequence similarity to VEGF-A and described as a viral virulence factor that appears to be derived from captured host genes. All eight cysteine residues of the central cysteine knot motif characteristic of members of the VEGF family are conserved among other residues in the VEGF-E proteins (Dehio et al., 1999; Wise et al., 1999). Alignment of all mammalian VEGF sequences indicated that VEGF-E is distinct from the previously described VEGFs but most closely related to VEGF-A. Like VEGF-A, VEGF-E was found to bind with high affinity to VEGF receptor-2 (KDR) resulting in receptor autophosphorylation, whilst in contrast to VEGF-A, VEGF-E can not bind to VEGF receptor-1 (Flt-1). Furthermore VEGF-E can also not bind to VEGF receptor-3 (FLT-4). Therefore VEGF-E is a potent angiog

The protein encoded by this gene is a member of the glial cell line-derived neurotophic factor (GDNF) family of ligands which are a group of ligands within the TGF-beta superfamily of signaling molecules. GDNFs are unique in having neurotrophic properties and have potential use for gene therapy in neurodegenrative disease. Artemin has been shown in culture to support the survival of a number of periferal neuron populations and at least one population of dopaminergic CNS neurons. Its role in the PNS and CNS is further substantiated by its expression pattern in the proximity of these neurons. This protein is a ligand for the RET receptor and uses GFR-alpha 3 as a coreceptor. Four alternatively spliced transcripts have been described, two of which encode the same protein.

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.

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 modules: Module 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.

TNFRSF13B (TACI) is a transmembrane receptor protein found predominantly on the surface of B cells (a significant part of the immune system). TACI was at first discovered owing to its ability to interact with calcium-modulator and cyclophilin ligand (CAML). Later on, it was found that TACI plays a key role in humoral immunity by interacting with two members of the TNF family. Also, TACI controls T cell-independent B cell antibody responses, isotype switching, and B cell homeostasis.

TNFR2 belongs to the TNF-receptor superfamily. TNFR2 is receptor with high affinity for TNFSF2/TNF-alpha and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. TNFR2 mediates the majority of the metabolic effects of TNF-alpha. In addition, knockout studies in mice propose a role for TNFR2 in protecting neurons from apoptosis by stimulating antioxidative pathways. TNFR2 expression might have a significant role in the angiogenesis, tumor cell proliferation and metastasis of Invasive micropapillary carcinoma of the breast.
There are 2 types of soluble TNF receptors: sTNFR-I and sTNFR-II, which act to neutralize the biological activities of TNF alpha and TNF beta. The levels of these soluble receptors seem to increase as a result of shedding of the extracellular domains of the membrane bound receptors. High levels of soluble TNF receptors are found in the amniotic fluid of pregnant women. TNFR2 and TNFR1 form a heterocomplex which mediates the recruitment of 2 anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. IAPs’ function in TNF-receptor signaling is unknown; nevertheless, c-IAP1 is believed to potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2, which mediates anti-apoptotic signals. Oxidative stress promotes TNFR1 and TNFR2 self-interaction, ligand-independent and enhanced ligand-dependent TNF signaling. TNF-a, TNFR1 and TNFR2 have roles in cellular differentiation. TNFR1 and TNFR2 function in cell type-specific renal injury.

Growth Differentiation Factor-7 (GDF-7) belongs to the BMP family of TGF-b superfamily proteins. GDF7 elicits its bioactivity via a heterodimeric receptor complex comprised of a type 1 (BMPR-IB) and a type II (BMPR-II or Activin RII) serine/threonine kinase receptor. GDF7 signaling results in the phosphorylation and activation of Smad proteins. GDF-7 is also involved in tendon and ligament formation and repair. In addition, GDF7 regulates bone formation, mesenchymal stem cell differentiation, neuronal differentiation, and axon guidance.

Glia Maturation Factor-Beta (GMF-Beta) is a 17 kDa protein nerve gorwth factor identified as a growth and differentiation factor in the vertebrate brain.
Glia Maturation Factor-Beta stimulates differentiation of normal neurons as well as glial cells. GMFB inhibits the proliferation of the N-18 neuroblastoma line and the C6 glioma line while promoting their phenotypic expression.
GMF-beta inhances the phenotypic expression of glia & neurons thus inhibits the proliferation of their respective tumors when added to cell culture. Although astrocytes produce GMF-b and stores it inside the cells, they don’t secrete the GMF-B into the cultured medium. Cell- surface GMFb acts on the target cells at close range when cells are in direct contact. GMF-Beta is produced by thymic epithelial cells and plays an important role in T cell development in favor of CD4+ T cells.
GMF-Beta is a brain-specific protein which belongs to the actin-binding proteins (ADF) family. GMF-beta appears to play a role in the differentiation, maintenance, and regeneration of the nervous system. It also supports the progression of certain auto-immune diseases, possibly through its ability to induce the production and secretion of various pro-inflammatory cytokines.

The somatomedins, or IGFs, comprise a family of peptides that play important roles in mammalian growth and development. IGF1 mediates many of the growth-promoting effects of GH. Early studies showed that GH did not directly stimulate the incorporation of sulfate into cartilage, but rather acted through a serum factor, termed 'sulfation factor,' which later became known as somatomedin. Three main somatomedins have been characterized: somatomedin C (IGF1), somatomedin A (IGF2), and somatomedin B.