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Epidermal growth factor receptor or EGFR or Erb-1 is a membranal protein that acts as a receptor for the extracellular EGF proteins family. This protein is a part of a family of receptors called ErbB family which are all tyrosine kinases receptors. Mutations in the gene of this receptors can cause cancer.

Tumor necrosis factor receptor superfamily member 8 (TNFRSF8) is a receptor for TNFSF8/CD30L. TNFRSF8 has a role in the regulation of cellular growth and transformation of activated lymphoblasts. In addition, the TNFRSF8 protein regulates gene expression via activation of NF-kappa-B. TNFRSF8 being a regulator of apoptosis, induces cell death or proliferation, depending on the cell type.

TNFR binds specifically to tumor necrosis factor (TNF) and blocks its interaction with cell surface TNF receptors. TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. It plays an important role in the inflammatory processes of rheumatoid arthritis (RA), polyarticular-course juvenile rheumatoid arthritis (JRA), and ankylosing spondylitis and the resulting joint pathology. In addition, TNF plays a role in the inflammatory process of plaque psoriasis. Elevated levels of TNF are found in involved tissues and fluids of patients with RA, psoriatic arthritis, ankylosing spondylitis (AS), and plaque psoriasis. Two distinct receptors for TNF (TNFRs), a 55 kilodalton protein (p55) and a 75 kilodalton protein (p75), exist naturally as monomeric molecules on cell surfaces and in soluble forms. Biological activity of TNF is dependent upon binding to either cell surface TNFR. Recombinant Human TNFR is a dimeric soluble form of the p75 TNF receptor that can bind to two TNF molecules.
It inhibits the activity of TNF in vitro and has been shown to affect several animal models of inflammation, including murine collagen-induced arthritis. TNFR inhibits binding of both TNF? and TNF? (lymphotoxin alpha [LT?]) to cell surface TNFRs, rendering TNF biologically inactive. Cells expressing transmembrane TNF that bind to TNFR are not lysed in vitro in the presence or absence of complement.
TNFR can also modulate biological responses that are induced or regulated by TNF, including expression of adhesion molecules responsible for leukocyte migration (i.e., E-selectin and to a lesser extent intercellular adhesion molecule-1 [ICAM-1]), serum levels of cytokines (e.g., IL-6), and serum levels of matrix metalloproteinase-3 (MMP-3 or stromelysin).

GMCSF is a cytokine that controls the production, differentiation, and function of granulocytes and macrophages. The active form of the protein is found extracellularly as a homodimer. This gene has been localized to a cluster of related genes at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. Other genes in the cluster include those encoding interleukins 4, 5, and 13.
GM-CSF stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes.

Human AIF1 protein shares 98% homology/identity with that of rat. AIF1 is expressed in macrophages and neutrophils. The expression of AIF1 transcripts is upregulated by IFN-g in rat macrophages. AIF1 is expressed selectively in human macrophage-like cell lines, and in a subset of CD68(+) macrophages in the interstitial and perivascular spaces of human heart allografts. In quiescent cultured human vascular smooth muscle cells synthesis of AIF1 is induced by IFN-g, IL1b, and conditioned medium of T-cells. Overexpression of AIF1 in human VSMCs results in enhanced growth of these cells. AIF1 is expressed during apoptosis rat mammary gland and ventral prostate tissues. Allograft Inflammatory Factor 1 is expressed by several tumor-associated activated macrophages and microglial cells in rat and human gliomas. There is an evident relationship of AIF1-expressing activated macrophages and microglial cells with tumor malignancy in humans.

Vascular endothelial growth factor is an important signaling protein involved in both vasculogenesis and angiogenesis. As its name implies, 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 this protein is linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in this gene have been associated with proliferative and nonproliferative diabetic retinopathy.

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.

CCL23 (MIP-3) is a ligand for the CCR1chemokine receptor. CCL23 is one of several cytokine genes clustered on the q-arm of chromosome 17, in a locus containing several other CC chemokines. MIP-3 chemoattracts monocytes, resting T-lymphocytes and neutrophils, but not activated lymphocytes. Furthermore, it was shown that MIP-3 inhibits colony formation of bone marrow myeloid immature progenitors. MIP-3 is mainly expressed in lung and liver tissue, but can be also found in bone marrow and placenta, as well as in some cell lines of myeloid origin.
Alternative splicing of the CCL23 gene produces 2 mRNAs which encode a short (CK?8) and a long (CK?81) isoform of the MIP-3. CK?8 cDNA encodes a 120 amino acid residue precursor protein with a putative 21 a.a. residue signal peptide which is cleaved to generate a 99 a.a. residue mature CK?8 (a.a. 22-120). Further N-terminal processing of the 99 a.a. residue variant can produce a 75 a.a. residue CK?8 (a.a. 46-120) which is considerably more active than the 99 a.a. residue variant.
MIP-3 may be involved in the malignant progression of certain human cancer cells which overexpress ErbB2 through the transactivation of ErbB2 tyrosine kinase. MIP-3 may also be involved in angiogenesis via upregulation of matrix metalloproteinase MMP-2 expression.

TFPI2 takes part in the regulation of plasmin-mediated matrix remodeling. Inhibits trypsin, plasmin, factor VIIa/tissue factor and weakly factor Xa. TFPI2 doesn’t have any influence on thrombin.

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.

GDF10 is a member of the BMP family and the TGF-beta superfamily. GDF10 is expressed in femur, brain, lung, skeletal, muscle, pancreas and testis, and has a role in head formation and possibly multiple roles in skeletal morphogenesis. In humans, GDF10 mRNA is found in the cochlea and lung of fetuses, and in testis, retina, pineal gland, and other neural tissues of adults. The BMP family members are regulators of cell growth and differentiation in both embryonic and adult tissues. These proteins are characterized by a polybasic proteolytic processing site which is cleaved to produce a mature protein containing 7 conserved cysteine residues.

Transforming Growth Factor Beta Induced protein also known as TGFBI is an extracellular matrix protein induced by transforming growth factor (TGF)-beta 1. TGFBI protein is involved in cell growth, cell differentiation, wound healing and cell adhesion. In addition, some missense mutations of TGFBI were identified in families affected with human autosomal dominant corneal dystrophies. TGFBI gene encodes for a 683 amino-acid protein containing an RGD motif and four internal repeated domains which have highly conserved sequences founded in several species (Fasciclin domain).

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.

EIF1B is critical for the scanning process in vitro. EIF1B is an element of a complex involved in recognition of the initiator codon during the scanning process. Translation is also initiated by the function of EIF1B in regulating the activity of ribosomal subunits 43S, 48S and 40S. EIF1B enables 43S ribosomal complexes to distinguish between cognate and near-cognate initiation codons, perceiving the nucleotide content of initiation codons.

Vascular endothelial growth factoris an important signaling proteininvolved in both vasculogenesisand angiogenesis. As its name implies, 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/macrophagemigration, 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 mitogenesisand cell migration. VEGF is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor.
Elevated levels of this protein is linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in this gene have been associated with proliferative and nonproliferative diabetic retinopathy.

IMPA2 is a member of the inositol monophosphatase family. IMPA2 catalyzes the dephosphoylration of inositol monophosphate and has a significant role in phosphatidylinositol signaling. IMPA2 can use the myo-inositol monophosphates, scylloinositol 1,4-diphosphate, glucose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates. IMPA2 is a pharmacological target for lithium Li(+) action in brain. IMPA2 is considered to have a role in schizophrenia and bipolar disorder.

TIMP2 belongs to the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases, a group of peptidases that take part in degradation of the extracellular matrix. Besides having an inhibitory role against metalloproteinases, the encoded protein has a exclusive part among TIMPfamily members in its capability to directly suppress the proliferation of endothelial cells. Consequently, the encoded protein is crucial to the conservation of tissue homeostasis by suppressing the production of quiescent tissues as an answer to angiogenic factors, and by inhibiting protease activity in tissues undergoing renovation of the extracellular matrix.

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.

The somatomedins, or insulin-like growth factors (IGFs), comprise a family of peptides that play important roles in mammalian growth and development. IGF1 mediates many of the 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). Three main somatomedins have been characterized: somatomedin C (IGF1), somatomedin A (IGF2; MIM 147470), and somatomedin B (MIM 193190) (Rotwein, 1986; Rosenfeld, 2003).

TRAF1 is an adapter protein and signal transducer that connects members of the TNFR family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. TRAF1 mediates activation of NF-kappa-B and JNK and participates in apoptosis. The TRAF1/TRAF2 complex recruits the apoptotic suppressors BIRC2 and BIRC3 to TNFRSF1B/TNFR2.

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.

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).

Vascular endothelial growth factor is an important signaling protein involved in both vasculogenesis and angiogenesis. As its name implies, 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/ macrophagemigration, 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 mitogenesisand cell migration. VEGF is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor.
Elevated levels of this protein are linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in this gene have been associated with proliferative and nonproliferative diabetic retinopathy.

Platelet factor-4 is a 70-amino acid protein that is released from the alpha-granules of activated platelets and binds with high affinity to heparin. Its major physiologic role appears to be neutralization of heparin-like molecules on the endothelial surface of blood vessels, thereby inhibiting local antithrombin III activity and promoting coagulation. As a strong chemoattractant for neutrophils and fibroblasts, PF4 probably has a role in inflammation and wound repair. Oncostatin-A is a member of the CXC chemokine family. Human PF4 is used for the proof of heparin-induced thrombocytopenia. Furthermore it is used as an inhibitor in the angiogenesis during tumor therapy.