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NGF-beta has nerve growth stimulating activity and the complex is involved in the regulation of growth and the differentiation of sympathetic and certain sensory neurons. Mutations in this gene have been associated with hereditary sensory and autonomic neuropathy, type 5 (HSAN5), and dysregulation of this gene's expression is associated with allergic rhinitis.

The clinical use of the potent anti-tumor activity of TNF-a has been limited by the proinflammatory side effects including fever, dose-limiting hypotension, hepatotoxicity, intravascular thrombosis, and hemorrhage. Designing clinically applicable TNF-a mutants with low systemic toxicity has been an intense pharmacological interest. Human TNF-a, which binds to the murine TNF-R55 but not to the mouse TNF-R75, exhibits retained anti-tumor activity and reduced systemic toxicity in mice compared with murine TNF-a, which binds to both murine TNF receptors. Based on these results, many TNF-? mutants that selectively bind to TNF-R55 have been designed. These mutants displayed cytotoxic activities on tumor cell lines in vitro, and exhibited lower systemic toxicity in vivo.
Recombinant Human TNF-a Variant/Mutant compared with the wild-type, has an amino acid sequence deletion from a.a. 1-7, and the following a.a. substitutes Arg8, Lys9, Arg10 and Phe157 which is proven tohave more activity and with less inflammatory side effect in vivo.

Geminin is a 25 kDa nuclear protein, which inhibits DNA replication and is degraded during the mitotic phase of the cell cycle. Geminin controls replication by binding to the licensing factor Cdt1, and is involved in neural differentiation. In addition, Geminin directly interacts with Six3 and Hox homeodomain proteins during embryogenesis and inhibits their functions. Geminin can also promote DNA replication. Geminin has 2 roles in 2 different stages of the cell cycle: Geminin is a negative regulator of DNA replication during the “S phase” of the cell cycle. Inhibition of Geminin during the “S phase” (by RNAi) results in an additional round of replication of portions of the genome. During the “M phase” of the cell cycle (mitosis) Geminin stabilizes the replication factor Cdt1 promoting DNA replication during the next cell cycle. Moreover, inhibition of Geminin during mitosis (by RNAi) causes destabilization of Cdt1 protein and impairment of DNA replication during the next cell cycle. Geminin thus guarantees that only one round of replication occurs during each cell cycle. It was discovered that Geminin is overexpressed in a number of malignancies and cancer cell lines. This maintains the concept that Geminin has also a positive role in DNA replication and cell cycle progression. Geminin accumulates through S, G2 and M phases of the cell cycle but is absent during the G1 phase. During the metaphase/anaphase transition of mitosis Geminin levels decrease.

Transforming growth factor betas (TGFBetas) mediate many cell-cell interactions which occur during embryonic development. Three TGFBetas have been identified in mammals. TGFBeta1, TGFBeta2 and TGFBeta3 are each synthesized as precursor proteins which are very similar in that each is cleaved to yield a 112 amino acid polypeptide which remains associated with the latent portion of the molecule.

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' (Daughaday et al., 1972). Three main somatomedins have been characterized: somatomedin C (IGF1), somatomedin A (IGF2; MIM 147470), and somatomedin B (MIM 193190) (Rotwein, 1986; Rosenfeld, 2003).

TRAIL Receptor-3, also known as TNFRSF10C belongs to theTNF-receptor super family. TNFRSF10C contains an extracellular TRAIL-binding domain as well as a transmembranedomain, however no cytoplasmic death domain. Furthermore, TNFRSF10C is not capable of inducing apoptosis, and is considered toact as an antagonistic receptor which protects cells from TRAIL-induced apoptosis.

The somatomedins, or insulin-like growth factors (IGFs), comprise a family of peptides that takes part in mammalian growth and development. IGF1 mediates various growth-promoting effects of growth hormone (GH; MIM 139250). Early studies showed that growth hormone 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' (Daughaday et al., 1972). 3 main somatomedins have been characterized: somatomedin C (IGF1), somatomedin A (IGF2; MIM 147470), and somatomedin B (MIM 193190) (Rotwein, 1986; Rosenfeld, 2003).

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. Long EGF is a recombinant analog of Human EGF developed as a replacement for use in therapeutic cell culture applications as a like-for-like supplement for Recombinant Human or native EGF. It includes the Human EGF amino acid sequence plus a 53 amino acid N-terminal extension peptide.

SDF-1 (stromal cell-derived factor-1) is small cytokine belonging to the chemokine family that is officially designated Chemokine (C-X-C motif) ligand 12 (CXCL12). It is produced in two forms, SDF-1?/CXCL12a and SDF-1?/CXCL12b, by alternate splicing of the same gene. Chemokines are characterized by the presence of four conserved cysteines, which form two disulfide bonds. The CXCL12 proteins belong to the group of CXC chemokines, whose initial pair of cysteines are separated by one intervening amino acid. CXCL12 is strongly chemotactic for lymphocytes and has been implicated as an important cell co-ordinator during development. During embryogenesis it directs the migration of hematopoietic cells from foetal liver to bone marrow. Mice which were knocked-out for CXCL12 gene were lethal before the birth or within just 1 hour of life. As another role, CXCL12a alters also the electrophysiology of neurons. CXCL12 was shown to be expressend in many tissues in mice (including brain, thymus, heart, lung, liver, kidney, spleen and bone marrow).
The receptor for this chemokine is CXCR4, which was previously called fusin. This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently it was suggested that CXCL12 is also bound by CXCR7 receptor.
The gene for CXCL12 is located on human chromosome 10. In human and mouse both CXCL12 and CXCR4 show high identity of sequence: 99% and 90%, respectively.

FGF8 is part of the fibroblast growth factor family. FGF family members have wide mitogenic and cell survival activities, and participate in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF8 supports androgen and anchorage independent growth of mammary tumor cells. FGF8 over expression increases tumor growth and angiogensis. The adult expression of FGF-8 gene is restricted to testes and ovaries. FGF8 functions as an embryonic epithelial factor. FGF8 takes part in midbrain and limb development, organogenesis, embryo gastrulation and left-right axis determination.

MANF is a 20kDa protein which belongs to the ARMET family. MANF was originally known as an arginine-rich region protein which was extremely mutated in a large number of tumors. MANF Expression is induced during ER stress, signifying that MANF takes part in protein quality control during ER stress.

Tumor necrosis factor is a member of a group of cytokines that all stimulate the acute phase reaction. TNF is involved in systemic inflammationand secreted mainly by macrophages.
TNF causes apoptotic cell death, cellular proliferation, differentiation, inflammation, tumorigenesis and viral replication, TNF is also involved in lipid metabolism, and coagulation. TNF's primary role is in the regulation of immune cells.
Dysregulation and, in particular, overproduction of TNF have been implicated in a variety of human diseases- autoimmune diseases, insulin resistance, and cancer.

TNFSF12 is a cytokine that is part of the TNF ligand family. TNFSF12 is a ligand for the FN14/TWEAKR receptor. TNFSF12 has overlapping signaling functions with TNF, but displays a much wider tissue distribution. TNFSF12 induces apoptosis through multiple pathways of cell death in a cell type-specific manner. TNFSF12 promotes proliferation and migration of endothelial cells, and therefore acts as a regulator of angiogenesis. TNFSF12 is expressed in adult heart, pancreas, skeletal muscle, small intestine, spleen and peripheral blood lymphocytes. TWEAK h induces NFkB and chemokine secretion. TNFSF12 exerts an apoptotic activity in HT-29 human adenocarcinoma cells whilst cultured in the presence of IFN-?. TNFSF12 promotes proliferation and migration of endothelial cells.

GH is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the gGH locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five GHs, leading to further diversity and potential for specialization. This particular family member is expressed in the pituitary but not in placental tissue as is the case for the other four genes in the GH locus. Mutations in or deletions of the gene lead to GH deficiency and short stature.

FGF-basic is a member of the fibroblast growth factor (FGF) family. FGF family members bind heparin and possess broad mitogenic and angiogenic activities. This protein has been implicated in diverse biological processes, such as limb and nervous system development, wound healing, and tumor growth. The mRNA for this gene contains multiple polyadenylation sites, and is alternatively translated from AUG and non-AUG (CUG) initiation codons resulting in five different isoforms with distinct properties. The CUG-initiated isoforms are localized in the nucleus and are responsible for the intracrine effect, whereas, the AUG-initiated form is mostly cytosolic and is responsible for the paracrine and autocrine effects of this FGF.
The heparin-binding growth factors are angiogenic agents in vivo and are potent mitogens for a variety of cell types in vitro. there are differences in the tissue distribution and concentration of these 2 growth factors.

Fibroblast Growth Factor 17 (FGF17) is a part of the fibroblast growth factor family. FGF family members have broad mitogenic and cell survival activities, and are involved in various biological processes includingmorphogenesis, embryonic development cell growth, , tissue repair, tumor growth and invasion. The FGF17 gene is highly expressed in the cerebellum and cortex. The mouse homolog of the FGF17 gene is localized to specific sites in the midline structures of the forebrain, the midbrain-hindbrain junction, developing skeleton and developing arteries, suggesting a part in central nervous system, bone and vascular development.

KGF-2 is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF-10 exhibits mitogenic activity for keratinizing epidermal cells, but essentially no activity for fibroblasts, which is similar to the biological activity of FGF7. Studies of the mouse homolog of suggested that this gene is required for embryonic epidermal morphogenesis including brain development, lung morphogenesis, and initiation of lim bud formation. This gene is also implicated to be a primary factor in the process of wound healing.

Rab GDP dissociation inhibitor beta isoform 1 (GDI2) is a member of the GDP dissociation inhibitors (GDIs) family. GDI proteins can bind and release GDP-bound Rab proteins from membranes. GDI1 interacts with virtually all of the Rab proteins, whereas GDI2 interacts with Rabll but not Rab3A. GDI2 distributes ubiquitously, presenting a membrane bound location in perinuclear regions of cells.

FGF-basic is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Three alternatively spliced variants encoding different isoforms have been described. The heparin-binding growth factors are angiogenic agents in vivo and are potent mitogens for a variety of cell types in vitro. There are differences in the tissue distribution and concentration of these 2 growth factors.

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.

FGF-23 is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF-23 inhibits renal tubular phosphate transport. The FGF-23 gene was identified by its mutations associated with autosomal dominant hypophosphatemic rickets (ADHR), an inherited phosphate wasting disorder. Abnormally high level expression of FGF-23 was found in oncogenic hypophosphatemic osteomalacia (OHO), a phenotypically similar disease caused by abnormal phosphate metabolism. FGF-23 mutations have also been shown to cause familial tumoral calcinosis with hyperphosphatemia.

KGF is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF7 is a potent epithelial cell-specific growth factor, whose mitogenic activity is predominantly exhibited in keratinocytes but not in fibroblasts and endothelial cells. Studies of mouse and rat homologs of this gene implicated roles in morphogenesis of epithelium, reepithelialization of wounds, hair development and early lung organogenesis.

KGF-2 is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF-10 exhibits mitogenic activity for keratinizing epidermal cells, but essentially no activity for fibroblasts, which is similar to the biological activity of FGF7. Studies of the mouse homolog of suggested that this gene is required for embryonic epidermal morphogenesis including brain development, lung morphogenesis, and initiation of lim bud formation. This gene is also implicated to be a primary factor in the process of wound healing.