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GHBP is a transmembrane receptor for growth hormone. Binding of growth hormone to the receptor leads to receptor dimerization and the activation of an intra- and intercellular signal transduction pathway leading to growth. A common alternate allele of this gene, called GHRd3, lacks exon three and has been well-characterized. Mutations in this gene have been associated with Laron syndrome, also known as the growth hormone insensitivity syndrome (GHIS), a disorder characterized by short stature. Other splice variants, including one encoding a soluble form of the protein (GHRtr), have been observed but have not been thoroughly characterized.

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 growth hormone 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 growth hormones, 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 growth hormone locus. Mutations in or deletions of the gene lead to growth hormone deficiency and short stature.

PEDF is a noninhibitory serpin with neurotrophic, anti-angiogenic, and anti-tumorigenic properties. PEDF is a 50,000 dalton glycoprotein created and secreted in many tissues all the way through the body. A key component of the anti-angiogenic action of PEDF is the induction of apoptosis in proliferating endothelial cells. Additionally, PEDF is capable to inhibit the activity of angiogenic factors such as VEGF and FGF-2. The neuro-protective effects of PEDF are achieved through suppression of neuronal apoptosis induced by peroxide, glutamate, or other neurotoxins. The recognition of a lipase-linked cell membrane receptor for PEDF (PEDF-R) that binds to PEDF with high affinity should facilitate further elucidation of the underlying mechanisms of this pluripotent serpin. To date, PEDF-R is the only signaling receptor known to be used by a serpin family member. The unique range of PEDF activities associate it as a potential therapeutic agent for the treatment of vasculature related neurodegenerative diseases such as age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR). PEDF in addition has the potential to be functional in the treatment of various angiogenesis-related diseases including a number of cancers.

ATF1, a cyclic-AMP dependent transcription factor, is expressed in a large selection of cell types and can dimerize with CREB. MSK1 and MSK2 protein kinases are essential for the stress-induced phosphorylation of transcription factors CREB and ATF1 in primary embryonic fibroblasts. Epidermal growth factor induction of c-jun expression needs ATF1 and MEF2 sites in the c-jun promoter.

Galectin-4 is a member of the subfamily of galectins composed of two carbohydrate recognition domains having similar peptide chains. The galectins are a family of beta-galactoside-binding proteins having a role in modulating cell-cell and cell-matrix interactions, which inhibits chronic inflammations, GVHD, and allergic responses. LGALS4 expression is limited to small intestine, colon, and rectum, and it is underexpressed in colorectal cancer. LGALS4 binds as an endogenous ligand to glycosphingolipids having 3-O-sulfated Gal residues and bind as well to cholesterol-3-sulfate. LGALS4 takes part in cell adhesion. LGALS4 plays a role in crosslinking the lateral cell membranes of the surface-lining epithelial cells, thus supporting epithelial integrity against mechanical stress exerted by the bowel lume. LGALS4 is in charge of intestinal inflammation via selective regulation of peripheral and mucosal T-cell cell cycle, in addition to cell death by apoptosis of T-cells by a pathway independent of the activation of caspases. LGALS4 blockade decreases TNF-alpha inhibitor induced T-cell death. LGALS4 decreases pro-inflammatory cytokine secretion including IL-6 & IL-17.

TXNDC12 is a member of the thioredoxin super family. This Family members have a thioredoxin fold with a consensus active-site sequence (CxxC) and take part in redox regulation, protection against oxidative stress, refolding of disulfide-containing proteins, and regulation of transcription factors.

Growth Hormone Binding Protein or GHR, is a protein, part of the cytokine receptor superfamily. GHR binds to 2 receptors, therefore it enhances signal transduction via dimerization of receptors. In elevated levels, growth hormone operates as an antagonist due to high variance in the binding sites affinities. The antagonist operation can be embellished even more when the binding site is reduced its affinity.

Vascular endothelial growth factor is an important signaling protein involved in both angiogenesis and vasculogenesis.VEGF activity has been mostly studied on cells of the vascular endothelium, although it does have effects on a number of other cell types (e.g. stimulation monocyte/macrophage migration, neurons, cancer cells, kidney epithelial cells ).VEGF mediates increased vascular permeability, induces angiogenesis, vasculogenesis and endothelial cell growth, promotes cell migration, and inhibits apoptosis. In vitro, VEGF has been shown to stimulate endothelial cell mitogenesis and cell migration. VEGF is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor.
Elevated levels of VEGF is linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in VEGF have been associated with proliferative and nonproliferative diabetic retinopathy.

TNF-related apoptosis-inducing ligand (TRAIL) is a ligand molecule which induces apoptosis. It is a type II transmembrane protein with homology to other members of the tumor necrosis factor family.
In humans, the gene that encodes for TRAIL is located at chromosome 3q26.
TRAIL binds to the death receptors, DR4 and DR5. The process of apoptosis is caspase-8-dependent. This protein preferentially induces apoptosis in transformed and tumor cells, but does not appear to kill normal cells although it is expressed at a significant level in most normal tissues.

Galectin-16 (LGALS16) binds lactose with high affinity. LGALS16 is a strong inducer of T-cell apoptosis.

The gene for TNFRSF12A was initially recognized as a fibroblast growth factor inducible immediate early response gene Fn14 in mouse NIH 3T3 fibroblasts. Human TNFRSF12A cDNA encodes a 129 amino acid residue type I transmembrane protein with a 27 aa signal peptide, a 53 aa extracellular domain, a 21 aa transmembrane domain and a 28 aa cytoplasmic domain. Human and mouse TNFRSF12A hold 82% aa sequence identity. TNFRSF12 is the tiniest member of the TNF receptor superfamily and has only one cysteine rich region in its extracellular domain. The TNFRSF12A cytoplasmic domain holds one TRAF binding motif which binds TRAFs 1, 2, and 3. TNFRSF12A binds its ligand TWEAK/TNFSF12A with high affinity to initiate a signal transduction cascade which subject to the cell type, causes different cellular responses such as cell death, cell proliferation, and angiogenesis.

BSND is a vital beta subunit for CLC chloride channels. These heteromeric channels are restricted to basolateral membranes of renal tubules and of potassium-secreting epithelia of the inner ear. BSND gene mutations are linked with Bartter syndrome with sensorineural deafness.

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.

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.

rGFP, also known as Green Fluorescent Protein, is a protein produced by the jellyfish (Aequorea Victoria) that produces bioluminescence in the green zone of the noticeable spectrum. Green Fluorescent Protein is a useful and ubiquitous instrument for producing chimeric proteins, where it functions as a fluorescent protein tag. rGFP is expressed in most known cell types and is used as a noninvasive fluorescent marker in living cells and organisms. Green Fluorescent Protein permits a broad range of applications where it has functioned as a cell lineage tracer, reporter of gene expression, or as a measure of protein-protein interactions.

Stem cell factor / KIT ligand (SCF) is a cytokine which binds CD117(c-Kit). SCF is also known as "steel factor" or "c-kit ligand". SCF exists in two forms, cell surface bound SCF and soluble (or free) SCF. Soluble SCF is produced by the cleavage of surface bound SCF by metalloproteases.
SCF is a growth factor important for the survival, proliferation, and differentiation of hematopoietic stem cells and other hematopoietic progenitor cells. One of its roles is to change the BFU-E (burst-forming unit-erythroid) cells, which are the earliest erythrocyte precursors in the erythrocytic series, into the CFU-E (colony-forming unit-erythroid).

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. This gene was identified by its mutations associated with autosomal dominant hypophosphatemic rickets (ADHR), an inherited phosphate wasting disorder. Abnormally high level expression of FGF23 was found in oncogenic hypophosphatemic osteomalacia (OHO), a phenotypically similar disease caused by abnormal phosphate metabolism. Mutations FGF23 have also been shown to cause familial tumoral calcinosis with hyperphosphatemia.

The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. Galectin-1 is an autocrine negative growth factor that regulates cell proliferation. Galectin-1 regulates cell apoptosis and cell differentiation. Galectin-1 binds CD45, CD3 and CD4 & inhibits CD45 protein phosphatase activity and therefore the dephosphorylation of lyn kinase. Galectin-1 and its ligands are one of the master regulators of immune responses as T-cell homeostasis and survival, T-cell immune disorders, inflammation and allergies as well as host–pathogen interactions. Galectin-1 expression or overexpression in tumors and/or the tissue surrounding them must be considered as a sign of the malignant tumor progression that is often related to the long-range dissemination of tumoral cells (metastasis), to their dissemination into the surrounding normal tissue, and to tumor immune-escape. Galectin-1 in its oxidized form plays a number of important roles in the regeneration of the central nervous system after injury. The targeted overexpression (or delivery) of Galectin-1 should be considered as a method of choice for the treatment of some kinds of inflammation-related diseases, neurodegenerative pathologies and muscular dystrophies. In contrast, the targeted inhibition of Galectin-1 expression is what should be developed for therapeutic applications against cancer progression. Galectin-1 is thus a promising molecular target for the development of new and original therapeutic tools. There is 88% homology between the human and mouse galectin-1.

NCF1 is a cytosolic subunit protein of neutrophil NADPH oxidase which a
Multi-component enzyme that is activates production of superoxide anion. NCF1, along with NCF2 and a membrane bound cytochrome b558, is necessary for activation of the latent NADPH oxidase necessary for superoxide production. Mutations in this NCF1 have been related with chronic granulomatous disease.

PEDF is a neurotrophic protein that induces extensive neuronal differentiation in retinoblastoma cells. SerpinF1 is a potent inhibitor of angiogenesis. EPC1 doesn’t undergo the stressed to relaxed conformation transition characteristic as of the active serpins since it exhibits no serine protease inhibitory activity.
Aqueous humour level of asymmetric dimethylarginine is correlated with PEDF in humans. ADMA and PEDF levels are increased in response to inflammation in uveitis.
Lack of PEDF expression is a potent factor for the enhancement of tumor growth and angiogenesis in breast cancer.
PEDF & VEGF genes contribute to the development of diabetic retinopathy.
PEDF and VEGF structural changes in blood vessel wall play an important role in the pathophysiology of PD patients.
PEDF-overexpressing tumors exhibited reduced intratumoral angiogenesis.
SerpinF1 is a new promising approach for the treatment of osteosarcoma.
Levels of the natural ocular anti-angiogenic factor SentrinF1 (PEDF) is associated with proliferative retinopathy.
VEGF secreted by retinal pigment epithelial cells upregulates PEDF expression via VEGFR-1 in an autocrine manner.
Sentrin-F1 concentration in the aqueous humor of diabetic patients predicts who will develop progression of retinopathy.
PEDF blocks angiogenic effects of leptin through its anti-oxidative properties.

Dimethylarginine dimethylaminohydrolase 1, is a part of the Dimethylarginine Dimethylaminohydrolase gene family. DDAH1 participates in nitric oxide generation by regulating cellular concentrations of methylarginines, that in turn inhibit nitric oxide synthase activity. Deficiency of DDAH1 results in ADMA (asymmetric dimethylarginine) increase and a decrease in cGMP generation.

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.