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ILK1 (Integrin-linked kinase) is a serine/threonine protein kinase, containing 4 ankyrin-like repeats. ILK1 regulates a number of biological properties which include: anchorage-independent cell cycle progression, tumor cell invasion and apoptosis. ILK1 can also be implicated in mediating cell architecture, adhesion to integrin substrates and anchorage-dependent growth in epithelial cells. Furthermore, ILK1 phosphorylates beta-1 and beta-3 integrin subunit on serine and threonine residues, but also AKT1 and GSK3B.
ILK1 interacts with the cytoplasmic domains of integrin ?1 and ?3 subunits in addition to several adaptors and signaling proteins, it also acts as a proximal receptor kinase regulating integrin-mediated signal transduction. ILK1 is a focal adhesion protein part of the complex ILK-PINCH. This complex is deemed to be one of the convergence points of integrin- and growth factor-signaling pathway. ILK1 is stimulated rapidly but briefly by both cell fibronectin interactions in a PI3-K-dependent manner, probably through the binding of PtdIns(3,4,5)P3 with a PH-like domain of ILK.
ILK1 over-expression has been documented in a wide variety of human malignancies.

CDKN2C is a member of the CDKN2 cyclin-dependent kinase inhibitor family. CDKN2C cooperates with CDK4 or CDK6, and inhibits the activation of the CDK kinases, therefore acts as a cell growth regulator which regulates cell cycle G1 progression. CDKN2C suppresses the cell growth and proliferation with a correlated dependency on endogenous retinoblastoma protein RB. Studies in the knockout mice show CDKN2C takes part in regulating spermatogenesis, in addition to suppressing tumorigenesis.

Kallikreins are a subgroup of serine proteases having various physiological functions. Numerous kallikreins are involved in carcinogenesis. Kallikrein-11 (KLK11) which is a multifunctional protease is 1 of the 15 kallikrein subfamily members found in a cluster on chromosome 19. KLK11 cleaves synthetic peptides after arginine but not lysine residues.

sRANK Receptor is a part of of the TNF superfamily of ligands and receptors which participates in the regulation of specific immunity and bone turnover. sRANK Receptor was originally acknowledged as a dendritic-cell-membrane protein, which by interacting with RANKL augments the capacity of dendritic cells to stimulate naive T cell proliferation and to endorse the survival of RANK and T cells. The full length human RANK cDNA encodes a type I transmembrane protein of 616 amino acids with a predicted 183 amino acid extracellular domain and a 383 amino acid cytoplasmic domain. sRANK Receptor is also expressed in a various tissues including skeletal muscle, thymus, liver, colon, small intestine and adrenal gland.

Prothrombin Complex Concentrate (PCC) is a combination of several blood clotting factors II, VII, IX and X. PCC is used in the treatment of the congenital bleeding disorders associated with Factors II, VII, IX, and X deficiencies. PCC reverses the effect of warfarin (a coumarin anti-coagulant) and is used in cases of significant bleeding in patients with a coagulopathy, for example, gastrointestinal haemorrhage or intracranial haemorrhage. The PCC is also extensively used in treating acquired coagulation abnormalities secondary to vitamin K deficiency, warfarin ingestion, and various types of liver disease.
Hepatitis, anaphylaxis and thrombosis have been reported as complications of prothrombin complex concentrates administration.

HINT1, also known as Histidine triad nucleotide-binding protein 1 is part of the superfamily named for a near C-terminal HXHXHXX motif (H:Histidine, X:a hydrophobic amino acid) positioned at the ?-phosphate of nucleotide substrates. HINT1 hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2. Though it was initially considered to be a protein kinase C inhibitor and act as a haplod-insufficient tumor suppressor including spontaneous tumor formation in Hint+/- and Hint-/- , its actual physiologic function is not known.

TNFRSF4, also known as TNF Receptor Superfamily Member 4, is a T cell co-stimulatory molecule which belongs to the TNF receptor superfamily. TNFRSF4 coordinates with other co-stimulatory substances such as CD28, CD40, CD30, CD27 and 4-1BB to control the activation of the immune response. TNFRSF4 takes a vital part in antigen-specific T cell expansion as well as survival. TNFRSF4 is up-regulated on CD4+ and CD8+ T cells upon engagement of the TCR by antigen presenting cells along with co-stimulation by CD40-CD40 Ligand and CD28-B7. In addition, TNFRSF4 regulates cytokine production from T cells, antigen presenting cells, natural killer cells and natural killer cells. TNFRSF4 regulates cytokine receptor signaling.

Tropomodulin 3 (TMOD3) is a member of the tropomodulin family. TMOD3 prevents the elongation and depolymerization of the actin filaments at the pointed end. Actin cytoskeleton regulation by filament capping proteins is essential to many dynamic cellular functions. TMOD3 functions as a negative regulator of cell migration; nevertheless the processes behind its cellular functions are unknown. The Tmod/TM complex influences the formation of the short actin protofilament, which sequentially outlines the geometry of the membrane skeleton.

Members of the Interferon regulatory factor (IRF) family regulate gene expression critical to immune response, hemopoiesis, and proliferation. IRF-3 is a member of the IRF family, and is distinct from other family members. Its transcriptional activity is regulated solely by posttranslational modifications. It plays a crucial role in activation of innate immunity and inflammation in response to viral infection. IRF-3 mediates interferon-stimulated response element (isre) promoter activation. Functions as a molecular switch for antiviral activity. Dsrna generated during the course of an viral infection leads to IRF3 phosphorylation on the c-terminal serine/threonine cluster. This induces a conformational change, leading to its dimerization, nuclear localization and association with creb binding protein (crebbp) to form dsrna-activated factor 1 (draf1), a complex which activates the transcription of genes under the control of isre. The complex binds to the ie and prdiii regions on the ifn

Full-length recombinant human neutrophil pro-collagenase (MMP-8), latent form.
Matrix metalloproteinase 8 (MMP-8), or neutrophil collagenase, degrades interstitial collagens, acting preferentially on collagen type I.
Increased full-length MMP-8 protein was associated with infiltration into the skin of neutrophils, which are the major cell type that expresses MMP-8.
MMP-8 is synthesized and stored in specific granules in neutrophil leukocytes. MMP-8 activity is therefore regulated by factors such as surface-bound ligands (IgG or complement components) that release it through degranulation.Once released and activated through proteolytic or oxidative mechanisms, MMP-8 plays a major role in the connective tissue turnover that accompanies inflammatory processes.

Cardiotrophin 1 (CT-1) is a 201 amino acid member of the interleukin-6 superfamily. It was identified by its ability to induce hypertrophic response in cardiac myocytes. CT-1 mRNA levels were found both in cardiac myocytes and in cardiac nonmyocytes. CT 1 was also detected in abundance in normal adult human lung and was expressed in both fetal and adult airway smooth muscle cells. CT 1 activates gp130 dependent signaling and stimulates the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway to transduce hypertrophic and cytoprotective signals in cardiac myocytes.
CT 1 has also a neurotrophic function. CTF1 deficiency causes increased motoneuron cell death in spinal cord and brainstem nuclei of mice during a period between embryonic day 14 and the first postnatal week. Moreover, CT-1 is a hepatocyte survival factor that efficiently reduces hepatocellular damage in animal models of acute liver injury. Cardiotrophin 1 expression is augmented after hypoxic stimulation and it can protect cardiac cells when added either prior to simulated ischaemia or at the time of reoxygenation following simulated ischaemia. Cardiotrophin 1 can induce expression of the protective heat shock proteins (hsps) in cardiac cells.
Cardiotrophin-1 increased ventricular expression of ANP, brain natriuretic peptide (BNP) and angiotensinogen mRNA.
Cardiophin 1 levels were significantly elevated in patients with heart failure, patients with dilatative cardiomyopathy, moderate/severe mitral regurgitation, stable and unstable angina and after acute myocardial infarction.

CB1 cannabinoid receptor-interacting protein 1 (CNRIP1) is a 164 amino acid protein and G-protein coupled receptor which is a member of the CNRIP family. The CNRIP1 interacts with the C-terminal tail of cannabinoid receptor 1. CNRIP1 is expressed in the brain tissue and, at low levels, in the testis. CNRIP1 is involved in appetite, synaptic plasticity, neuroprotection and analgesia.

Endothelial cells express three different vascular endothelial growth factor (VEGF) receptors, belonging to the family of receptor tyrosine kinases (RTKs). They are named VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), VEGFR-3 (Flt-4). Their expression is almost exclusively restricted to endothelial cells, but VEGFR-1 can also be found on monocytes. All VEGF-receptors have seven immunoglobulin-like extracellular domains, a single transmembrane region and an intracellular split tyrosine kinase domain. VEGFR-2 has a lower affinity for VEGF than the Flt-1 receptor, but a higher signaling activity. Mitogenic activity in endothelial cells is mainly mediated by VEGFR-2 leading to their proliferation.
Differential splicing of the flt-1 gene leads to the formation of a secreted, soluble variant of VEGFR-1 (sVEGFR-1). No naturally occuring, secreted forms of VEGFR-2 have so far been reported. The binding of VEGF165 to VEGFR-2 is dependent on heparin.

Basic fibroblast growth factor 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 (TGF Betas) mediate many cell-cell interactions that occur during embryonic development. Three TGF Betas have been identified in mammals. TGF Beta 1, TGF Beta 2 and TGF Beta 3 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.

Transforming growth factor betas (TGF Betas) mediate many cell-cell interactions that occur during embryonic development. Three TGF Betas have been identified in mammals. TGF Beta 1, TGF Beta 2 and TGF Beta 3 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.

FIAF (fasting-induced adipose factor) a.k.a ANGPTL4 or PGAR or HFARP is an adipocytokine up-regulated by fasting, by peroxisome proliferator-activated receptor agonists, and by hypoxia. ANGPTL4 is found in human and mouse blood plasma both as a native protein and in a truncated form. In human white adipose tissue and SGBS adipocytes, only the native form of ANGPTL4 could be detected, whereas in mice the differentiation of mouse 3T3-L1 adipocytes is associated with the production of truncated ANGPTL4. However, the truncated ANGPTL4 is produced by human liver. In human blood plasma FIAF is mainly presented in a truncated form (FIAF-S2), whose levels treatment increases (as shown by experimental data). There is an inter individual variation in ANGPTL4 levels of both the truncated and the native form, however those levels were not influenced by prolonged semistarvation and are not associated with body mass index.

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.

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.

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.

VEGF-C, also known as Vascular Endothelial Growth Factor Related Protein (VRP), is a recently discovered VEGF growth factor family member that is most closely related to VEGF-D. Human VEGF-C cDNA encodes a pre-pro-protein of 416 amino acids residues. It is almost identical to the mouse VEGF-C protein. Similar to VEGF-D, VEGF-C has a VEGF homology domain spanning the middle third of the precursor molecule and long N- and C-terminal extensions. In adults, VEGF-C is highly expressed in heart, placenta, ovary and small intestine. Recombinant human VEGF-C, lacking the N- and C-terminal extensions and containing only the middle VEGF homology domain, forms primarily non-covalently linked dimers. This protein is a ligand for both VEGFR-2/KDR and VEGFR-3/FLT-4. Since VEGFR-3 is strongly expressed in lymphatic endothelial cells, it has been postulated that VEGF-C is involved in the regulation of the growth and/or differentiation of lymphatic endothelium. Although recombinant human VEGF-C is also a mitogen for vascular endothelial cells, it is much less potent than VEGF-A.

Prolactin is a lactogenic hormone secreted by the adenohypophysis .Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation.Prolactin has been shown also to have cytokine-like activities and to have important immunoregulatory activities. It contributes to the development of lymphoid tissues and the maintenance of physiological immune function and also modulates a variety of T-cell immune responses. Prolactin has been reported to activate cellular proliferation in nonreproductive tissue, such as liver, spleen, and thymus. It induces significant proliferation in aortic smooth muscle cells and also enhances proliferation of these cells induced by PDGF . Prolactin also appears to be directly mitogenic for pancreatic beta cells. Prolactin is also mitogenic for cultured astrocytes.