growth-regulated a protein

GHR Growth Hormone R Protein, Mouse, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 30.3 kDa and the accession number is Q3UP14.

GHR Growth Hormone R Protein, Rat, Recombinant (hFc) is expressed in HEK293 mammalian cells with hFc tag. The predicted molecular weight is 55.4 kDa and the accession number is P16310-1.

Pegvisomant, a growth hormone receptor (GHR) antagonist, is a well-known drug that was designed to treat acromegaly. However, recent studies have indicated that the GHR is a moonlighting protein that may exhibit dual functions based on its localization in the plasma membrane and nucleus.

Growth Hormone Protein, Human, Recombinant is expressed in E. coli expression system. The predicted molecular weight is 22.1 kDa and the accession number is P01241.

Growth hormone receptor is a transmembrane receptor for growth hormone (GH). GH is a single-chain polypeptide that is mainly synthesized and released from the anterior pituitary gland and plays essential roles in growth, development and metabolism. GH exerts its physiological actions via GH binding to its receptor in its extracellular domain. 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. Growth hormone receptor has been shown to interact with SGTA, PTPN11, Janus kinase 2, Suppressor of cytokine signaling 1 and CISH.

Somatotropin(GH) is a member of the somatotropin prolactin family of hormones which play an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. GH stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.

Growth Hormone Protein, Human, Recombinant (His) is expressed in E. coli expression system with His tag. The predicted molecular weight is 24.7 kDa and the accession number is P01241.

GHR Growth Hormone R Protein, Mouse, Recombinant (His & hFc) is expressed in HEK293 mammalian cells with His and hFc tag. The predicted molecular weight is 56.8 kDa and the accession number is Q3UP14.

GHR Growth Hormone R Protein, Rat, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 29.6 kDa and the accession number is P16310-1.

CCN4 Wnt-induced secreted protein 1 (WISP1) is a secreted, cysteine-rich, heparin-binding glycoprotein, belonging to the CCN (CTGF CYR61 NOV) family of growth factors, and is involved in diverse biological functions such as cell growth, adhesion, migration, angiogenesis, tissue repair, and regulation of extracellular matrix. Members of the CCN family demonstrate high structural homology sharing four conserved cysteine-rich modular domains: an IGFBP (insulin-like growth factor-binding) domain, a von Willebrand type C domain, a thrombospondin domain and a C-terminal cysteine -knot domain. WISP1 is a putative downstream effector of the Wnt Frizzled pathway that mediates diverse developmental processes, was identified as an oncogene regulated by the Wnt-1-beta-catenin pathway. Thus WISP1 may contribute to Wnt-1-mediated tumorigenesis and malignance. Expression of WISP1 in some cells results in transformation and tumorigenesis. WISP1 acts to block cell death at a late stage in the p53-mediated apoptosis pathway. It was reported that WISP1 interacts with sulfated glycoconjugates, decorin and biglycan in the ECM of connective tissue, and possibly prevents their inhibitory activity in tumor cell proliferation.

DEP1 PTPRJ (Receptor-type tyrosine-protein phosphatase eta) is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes, including cell growth, differentiation, mitotic cycle, and oncogenic transformation. DEP1 PTPRJ possesses an extracellular region containing five fibronectin type III repeats, a single transmembrane region, and a single intracytoplasmic catalytic domain, and thus represents a receptor-type PTP. DEP1 PTPRJ is present in all hematopoietic lineages, and was shown to negatively regulate T cell receptor signaling possibly through interfering with the phosphorylation of Phospholipase C Gamma 1 and Linker for Activation of T Cells. This protein can also dephosphorylate the PDGF beta receptor, and may be involved in UV-induced signal transduction. In stable MCF-7 cell lines, induction of DEP-1 expression inhibited breast cancer cell growth by 5-10-fold. These data describe PTPs expressed and regulated in breast cancer cell lines during differentiation and identify one PTP, DEP-1, that inhibits the growth of breast cancer cells in vitro.

Vasorin is a typical type I membrane protein. It contains 1 EGF-like domain, 1 fibronectin type-III domain, 10 LRR (leucine-rich) repeats, 1 LRRCT domain and 1 LRRNT domain. Vasorin is predominantly expressed in vascular smooth muscle cells, and that its expression is developmentally regulated. vasorin It directly binds to transforming growth factor (TGF)-β and attenuates TGF-β signaling in vitro. This suggests that down-regulation of vasorin expression contributes to neointimal formation after vascular injury and that vasorin modulates cellular responses to pathological stimuli in the vessel wall.

GAS6 (Growth arrest-specific protein 6) is also known as AXL receptor tyrosine kinase ligand, AXLLG, is a multimodular protein that is up-regulated by a wide variety of cell types in response to growth arrest. Gas6 binds and induces signaling through the receptor tyrosine kinases Axl, Dtk, and Mer whose signaling is implicated in cell growth and survival, cell adhesion and cell migration. GAS6 AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses.

Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2 SMAD4 complex, activates transcription. May act as a tumor suppressor in colorectal carcinoma. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.

EBP1, also known as PA2G4, is an RNA-binding protein that belongs to the peptidase M24 family. It can be detected n several cell lines tested, including primary and transformed cell lines. EBP1 also present in pre-ribosomal ribonucleoprotein complexes and may be involved in ribosome assembly and the regulation of intermediate and late steps of rRNA processing. This protein is a transcriptional co-repressor of androgen receptor-regulated genes and other cell cycle regulatory genes through its interactions with histone deacetylases. PA2G4 can interact with the cytoplasmic domain of the ErbB3 receptor and may contribute to transducing growth regulatory signals. EBP1 has been implicated in growth inhibition and the induction of differentiation of human cancer cells. It seems to be involved in growth regulation. EBP1 also mediates cap-independent translation of specific viral IRESs (internal ribosomal entry site).

DCBLD2, also known as ESDN and CLCP1, localizes in various compartments. DCBLD2 is up-regulated in lung cancers and is regulated by transcription factor AP-2 alpha (TFAP2A), a component of activator protein-2 (AP-2) that is known to regulate IL-8 production in human lung fibroblasts and epithelial cells. DCBLD2 could be related to FEV(1)-related phenotypes in asthmatics. DCBLD2 gene is expressed at very high level. DCBLD2 is proposed to participate in processes such as intracellular receptor mediated signaling pathway, negative regulation of cell growth and so on.

Striated muscle preferentially expressed protein kinase, also known as aortic preferentially expressed protein 1, APEG-1, SPEG and KIAA1297, is a protein that belongs to the protein kinase superfamily and CAMK Ser Thr protein kinase family. SPEG APEG-1 contains two fibronectin type-III domains, nine Ig-like (immunoglobulin-like) domains, two protein kinase domains. Isoform 1 of SPEG is preferentially expressed in striated muscle. Non-kinase form such as isoform 3 of SPEG is predominantly expressed in the aorta. Isoform 3 of SPEG appears to be expressed only in highly differentiated ASMC in normal vessel walls and down-regulated in dedifferentiated ASMC. Isoform 3 of SPEG may have a role in regulating the growth and differentiation of arterial smooth muscle cells. Isoform 3 of SPEG is quickly down-regulated in response to vascular injury, when ASMC cells change from a quiescent to a proliferative phenotype.

Calmodulin-Dependent Protein Kinase (CaM Kinase) is a kind of protein phosphorylate multiple downstream targets. Concentration of cytosolic calcium functions as a second messenger that mediates a wide range of cellular responses. Calcium binds to calcium binding proteins (calmodulin CaM) and stimulates the activity of a variety of enzymes, including CaM kinases referred to as CaM-kinases (CaMKs), such as CaMKI, CaMKII, CaMKIV and CaMKK. Calmodulin-dependent protein kinase CL3 CaMKIγ is a memberane-anchored CaMK belonging to the CaM kinase family. Its C-terminal region is uniquely modified by two sequential lipidification steps: prenylation followed by a kinase-activity-regulated palmitoylation. These modifications are essential for CaMKIγ membrane anchoring and targeting into detergent-resistant lipid microdomains in the dendrites. It has been found that CaMKIγ critically contributed to BDNF-stimulated dendritic growth. Raft insertion of CaMKIγ specifically promoted dendritogenesis of cortical neurons by acting upstream of RacGEF STEF and Rac, both present in lipid rafts. Thus, CaMKIγ may represent a key element in the Ca2+-dependent and lipid-raft-delineated switch that turns on extrinsic activity-regulated dendrite formation in developing cortical neurons.

NOTCH2 (Notch Receptor 2) is a Protein Coding gene. This gene encodes a member of the Notch family. Members of this Type 1 transmembrane protein family share structural characteristics and play a role in a variety of developmental processes by controlling cell fate decisions. Hajdu Cheney Syndrome (HCS) is a rare disease associated with mutations of NOTCH2 that lead to the translation of a truncated, presumably stable, NOTCH2 protein. NOTCH2 is down-regulated in colon cancer, and reduced expression is associated with a less differentiated, more aggressive phenotype, and reduced overall survival. NOTCH2 has also been shown to have pro-apoptotic and growth-suppressive effects in thyroid carcinoma, and carcinoid tumors. NOTCH2 acts as an oncogene that promotes bladder cancer growth and metastasis through EMT, cell-cycle progression, and maintenance of stemness.

GAS6 (Growth arrest-specific protein 6) is also known as AXL receptor tyrosine kinase ligand, AXLLG, is a multimodular protein that is up-regulated by a wide variety of cell types in response to growth arrest. Gas6 binds and induces signaling through the receptor tyrosine kinases Axl, Dtk, and Mer whose signaling is implicated in cell growth and survival, cell adhesion and cell migration. GAS6 AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. GAS6 Protein, Human, Recombinant (His) is expressed in HEK293 cells.

Cartilage Oligomeric Matrix Protein (COMP), also referred to as Thrombospondin-5, is a non-collagenous extracellular matrix (ECM) protein and belongs to the subgroup B of the thrombospondin protein family. This protein is expressed primarily in cartilage, ligament, and tendon, and binds to other ECM proteins such as collagen I, II and IX with high affinities depending on the divalent cations Zn2+ or Ni2+. COMP is a secreted glycoprotein that is important for growth plate organization and function. It is suggested to play a role in cell growth and development, and recent studies have revealed the possible mechanism that it protects cells against death by elevating members of the IAP (inhibitor of apoptosis protein) family of survival proteins. Mutations in COMP cause two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1), and up-regulated expression of COMP are observed in rheumatoid arthritis and certain carcinomas.

CNTNAP2 CASPR2 is a member of the neurexin family which functions in the vertebrate nervous system as cell adhesion molecules and receptors. This protein, like other neurexin proteins, contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5 8 type C domain, discoidin neuropilin- and fibrinogen-like domains, thrombospondin N-terminal-like domains and a putative PDZ binding site. CNTNAP2 CASPR2 is localized at the juxtaparanodes of myelinated axons, and mediates interactions between neurons and glia during nervous system development and is also involved in localization of potassium channels within differentiating axons. This protein encoding gene is directly bound and regulated by forkhead box protein P2 (FOXP2), a transcription factor related to speech and language development. This gene has been implicated in multiple neurodevelopmental disorders, including Gilles de la Tourette syndrome, schizophrenia, epilepsy, autism, ADHD and mental retardation. CNTNAP2 CASPR2 may play a role in the formation of functional distinct domains critical for saltatory conduction of nerve impulses in myelinated nerve fibers. CNTNAP2 CASPR2 Seems to demarcate the juxtaparanodal region of the axo-glial junction.

Acetylcholinesterase, also known as ACHE, is an enzyme that degrades (through its hydrolytic activity) the neurotransmitter acetylcholine, producing choline and an acetate group. Acetylcholinesterase plays a crucial role in nerve impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter acetylcholine (ACh). ACHE appears to be a potential therapeutic target at muscle injuries including organophosphate myopathy. It is an externally oriented membrane-bound enzyme and its main physiological role is termination of chemical transmission at cholinergic synapses and secretory organs by rapid hydrolysis of the neurotransmitter acetylcholine (ACh). ACHE plays important roles in the cholinergic system, and its dysregulation is involved in a variety of human diseases. ACHE was significantly down-regulated in the cancerous tissues of 69.2% of hepatocellular carcinoma (HCC) patients, and the low ACHE expression in HCC was correlated with tumor aggressiveness, an elevated risk of postoperative recurrence, and a low survival rate. Both the recombinant ACHE protein and the enhanced expression of ACHE significantly inhibited HCC cell growth in vitro and tumorigenicity in vivo. ACHE as a tumor growth suppressor in regulating cell proliferation, the relevant signaling pathways, and the drug sensitivity of HCC cells. Thus, ACHE is a promising independent prognostic predictor for HCC recurrence and the survival of HCC patients. ACHE is responsible for the hydrolysis of acetylcholine in the nervous system. It is inhibited by organophosphate and carbamate pesticides. However, this enzyme is only slightly inhibited by organophosphorothionates.

Serine threonine-protein kinase SRPK3, also known as Muscle-specific serine kinase 1, Serine arginine-rich protein-specific kinase 3, SR-protein-specific kinase 3, Serine threonine-protein kinase 23, MSSK-1, SRPK3 and MSSK1, is a member of the protein kinase superfamily and CMGC Ser Thr protein kinase family. SRPK3 is a protein kinase belonging to serine arginine protein kinases (SRPK) family, which phosphorylates serine arginine repeat-containing proteins, and is controlled by a muscle-specific enhancer directly regulated by MEF2. SRPK3 MSSK1 contains one protein kinase domain. SRPK3 MSSK1 is exclusively expressed in skeletal and heart muscle. It is required for normal muscle development. Myocyte enhancer factor 2 (MEF2) plays essential roles in transcriptional control of muscle development. Normal muscle growth and homeostasis require MEF2-dependent signaling by SRPK3.

Serine threonine-protein kinase TAO3, also known as cutaneous T-cell lymphoma-associated antigen HD-CL-9, CTCL-associated antigen HD-CL-9, Dendritic cell-derived protein kinase, JNK SAPK-inhibitory kinase, Jun kinase-inhibitory kinase, Kinase from chicken homolog A, Thousand and one amino acid protein 3, JIK, TAOK3 and MAP3K18, is cytoplasm and peripheral membrane protein which belongs to the protein kinase superfamily, STE Ser Thr protein kinase family and STE2 subfamily. Protein kinases are pivotal regulators of cell signaling that modulate each other's functions and activities through site-specific phosphorylation events. TAOK3 JIK contains one protein kinase domain. TAOK3 JIK is ubiquitously expressed at a low level, and highly expressed in peripheral blood leukocytes (PBLs), thymus, spleen, kidney, skeletal muscle, heart and liver. TAOK3 JIK inhibits the basal activity of Jun kinase. It is negatively regulated by epidermal growth factor (EGF). When overexpressed, TAOK3 JIK may activate ERK1 ERK2 and JNK SAPK.

Growth-regulated alpha protein (CXCL1,KC), is a member of the alpha chemokine subfamily, was initially identified as an immediate early gene induced in mouse fibroblasts by platelet-derived growth factor. The N-terminal processed form KC(5-72) of the protein is produced by proteolytic cleavage after secretion from bone marrow stromal cells, and shows a highly enhanced hematopoietic activity. Mouse KC shows approximately 63% identity to that of mouse MIP-2. KC is also approximately 60% identical to the human GROs. It has been suggested that mouse KC and MIP-2 are the orthologs of the human GROs and rat CINCs. Cxcl1 has chemotactic activity for neutrophils, and contributes to neutrophil activation during inflammation. Hematoregulatory chemokine, in vitro, suppresses hematopoietic progenitor cell proliferation.

C-Kit SCF R is a type 3 transmembrane receptor for MGF (mast cell growth factor, also known as stem cell factor). c-Kit contains 5 Ig-like C2-type (immunoglobulin-like) domains and 1 protein kinase domain. It belongs to the protein kinase superfamily and CSF-1 PDGF receptor subfamily. SCF R expression on mast cells enables them to infiltrate SCF-secreting tumors where they promote tumor growth and induce local immune suppression. SCF R is up-regulated on dendritic cells by Th2-orTh17-biasing stimuli, and it is required for subsequent dendritic cell induction of Th2 and Th17 responses. SCF R protects vascular smooth muscle cells from apoptosis and assists in the recovery of cardiac function following myocardial infarction.

Vasorin is a Type I membrane protein, which is predominantly expressed in vascular smooth muscle cells in a developmentally regulated pattern. The expression level of Vasorin can be down regulated during vessel repair after arterial injury. Vasorin binds to transforming growth factor beta (TGF-β) and attenuates TGF-β signaling in vitro.

Fibroblast growth factor 4(FGF-4) is a heparin binding member of the FGF family. The human FGF4 cDNA encodes 206 amino acids (aa) with a 33 aa signal sequence and a 173 aa mature protein with an FGF homology domain that contains a heparin binding region near the C-terminus. Mature human FGF4 shares 91%, 82%, 94% and 91% aa identity with mouse, rat, canine and bovine FGF4, respectively. Human FGF-4 has been shown to exhibit cross species activity. Expression of FGF-4 and its receptors, FGF R1c, 2c, 3c and 4, is spatially and temporally regulated during embryonic development. FGF-4 is proposed to play a physiologically relevant role in human embryonic stem cell selfrenewal. It promotes stem cell proliferation, but may also aid differentiation depending on context and concentration, and is often included in embryonic stem cell media in vitro. FGF-4 is mitogenic for fibroblasts and endothelial cells in vitro and has autocrine transforming potential. It is a potent angiogenesis promoter in vivo and has been investigated as therapy for coronary artery disease.

Bone Morphogenetic Protein 5 (BMP-5) is a member of the structurally and functionally related bone morphogenetic proteins (BMPs) which constitute a novel subfamily of the transforming growth factor β (TGF-β) superfamily. In agreement with a possible role in the control of cell death, BMP-5 exhibited a regulated pattern of expression in the interdigital tissue. Transcripts of BMP-5 and BMP-5 protein were abundant within the cytoplasm of the fragmenting apoptotic interdigital cells in a way suggesting that delivery of BMPs into the tissue is potentiated during apoptosis. Gain-of-function experiments demonstrated that BMP-5 has the same effect as other interdigital BMPs inducing apoptosis in the undifferentiated mesoderm and growth in the prechondrogenic mesenchyme. BMP-5 is a member of the 60A subgroup of BMPs, other members of which have been shown to stimulate dendritic growth in central and peripheral neurons. The signaling pathway that mediates the dendrite-promoting activity of BMP-5 may involve binding to BMPR-IA and activation of Smad-1, and relative levels of BMP antagonists such as noggin and follistatin may modulate BMP-5 signaling. Since BMP-5 is expressed at relatively high levels not only in the developing but also the adult nervous system, these findings suggest the possibility that BMP-5 regulates dendritic morphology not only in the developing but also the adult nervous system. BMP-5 may play important roles not only in myocardial differentiation but also in the formation and maintenance of endocardial cushion tissue. Additionally, a high expression level of BMP-5 has been detected in certain tumors of mesenchymal origin.

Chloride intracellular channel protein 4, also known as Intracellular chloride ion channel protein p64H1 and CLIC4, is a member of the chloride channel CLIC family. It contains oneGST C-terminal domain. CLIC4 is a member of a family of intracellular chloride channels. It is regulated by p53, c-Myc, and tumor necrosis factor-alpha. CLIC4 is detected in epithelial cells from colon, esophagus and kidney (at protein level). CLIC4 has alternate cellular functions like a potential role in angiogenesis or in maintaining apical-basolateral membrane polarity during mitosis and cytokinesis. CLIC4 could promote endothelial cell proliferation and regulate endothelial morphogenesis (tubulogenesis). Expression of CLIC4 is prominent in heart, kidney, placenta and skeletal muscle. Overexpression of CLIC4 in cancer cells inhibits tumor growth. Conversely, overexpression of CLIC4 in tumor stromal cells stimulates tumor growth. Thus, CLIC4 participates in normal and pathological processes and may serve as a useful target for therapies in disturbances of homeostasis and neoplastic transformation. Loss of CLIC4 in tumor cells and gain in tumor stroma is common to many human cancers and marks malignant progression. Up-regulation of CLIC4 in tumor stroma is coincident with myofibroblast conversion, generally a poor prognostic indicator. Reactivation and restoration of CLIC4 in tumor cells or the converse in tumor stromal cells could provide a novel approach to inhibit tumor growth.

IDO2 belongs to the indoleamine 2,3-dioxygenase family. Indoleamine 2,3-dioxgyenase (IDO), is a cytosolic haem protein which, together with the hepatic enzyme tryptophan 2,3-dioxygenase, catalyzes the conversion of tryptophan and other indole derivatives to kynurenines. In addition to classic IDO (IDO1), a new variant, IDO2, has recently been described. IDO2 is expressed in the liver, small intestine, spleen, placenta, thymus, lung, brain, kidney, and colon. IDO is widely distributed in human tissues, its physiological role is not fully understood but is of great interest. IDO can be up-regulated via cytokines such as interferon-gamma, and can thereby modulate the levels of tryptophan, which is vital for cell growth. In humans and mice, the IDO1 and IDO2 genes are present tandemly in a tail-to-head arrangement on chromosome 8. In lower vertebrates such as zebrafish and toads, only a single IDO gene may be present that may be more IDO2-like in structure. This closer relationship to IDO2 suggests that IDO2 may be the ancestor of the better characterized IDO1 gene and that IDO1 might have been generated by gene duplication of IDO2 before the origin of tetrapods in mammalian evolutionary history. IDO2 catalyzes the first and rate-limiting step in the kynurenine pathway of tryptophan catabolism.

Ribosomal protein S6 kinase alpha-2, also known as 9 kDa ribosomal protein S6 kinase 2, MAP kinase-activated protein kinase 1c, MAPK-activated protein kinase 1c, Ribosomal S6 kinase 3, RSK-3, RPS6KA2 and MAPKAPK1C, is a nucleus protein that belongs to the protein kinase superfamily, AGC Ser Thr protein kinase family and S6 kinase subfamily. RPS6KA2 RSK-3 is expressed in many tissues. Highest expression is in lung and skeletal muscle. The expression of RPS6KA2 reduced proliferation, caused G1 arrest, increased apoptosis, reduced levels of phosphorylated extracellular signal-regulated kinase and altered other cell cycle proteins. RPS6KA2 RSK-3 contains one AGC-kinase C-terminal domain and two protein kinase domains. It forms a complex with either ERK1 or ERK2 in quiescent cells. It transiently dissociates following mitogenic stimulation. RPS6KA2 RSK-3 is a serine threonine kinase that may play a role in mediating the growth-factor and stress induced activation of the transcription factor CREB. RPS6KA1, RPS6KA2, RPS6KB1, RPS6KB2, and PDK1 are involved in several pathways central to the carcinogenic process, including regulation of cell growth, insulin, and inflammation.

Mothers against decapentaplegic homolog 3(SMAD3) is a cytoplasm protein which belongs to the dwarfin SMAD family. Smad proteins undergo rapid nuclear translocation upon stimulation by transforming growth factor and in so doing transduce the signal into the nucleus. Receptor-regulated SMAD is an intracellular signal transducer and transcriptional modulator activated by TGF-beta and activin type 1 receptor kinases. SMAD3 binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3 SMAD4 complex, activates transcription. It also can form a SMAD3 SMAD4 JUN FOS complex at the AP-1 SMAD site to regulate TGF-beta-mediated transcription. SMAD3 has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive.

Growth Arrest and DNA Damage-Inducible Protein GADD45 Υ (GADD45G) is a nuclear protein which belongs to the GADD45 family. GADD45G is highly expressed in placenta. GADD45G interacts with various proteins whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. GADD45G responds to environmental stresses by mediating activation of the p38 JNK pathway via MTK1 MEKK4 kinase. GADD45G is also involved in the regulation of growth and apoptosis. GADD45G inhibits cell growth and differentiation by androgens. The mRNA expression is down-regulated in hepatocellular carcinoma.

Biliverdin reductase (hBVR) is a serine threonine kinase that catalyzes reduction of the heme oxygenase (HO) activity product, biliverdin, to bilirubin. BVR consists of an N-terminal dinucleotide-binding domain (Rossmann-fold) and a C-terminal domain that contains a six-stranded β-sheet that is flanked on one face by several α-helices. The C-terminal and N-terminal domains interact extensively, forming the active site cleft at their interface. Biliverdin reductase (BVR) catalyzes the last step in heme degradation by reducing the γ-methene bridge of the open tetrapyrrole, biliverdin IXα, to bilirubin with the concomitant oxidation of a β-nicotinamide adenine dinucleotide (NADH) or β-nicotinamide adenine dinucleotide phosphate (NADPH) cofactor. It is now recognized that human BVR (hBVR) is a dual-specificity kinase (Ser Thr and Tyr) upstream activator of the insulin insulin growth factor-1 (IGF-1) and mitogen-activated protein kinase (MAPK) signaling pathways. Human BVR (hBVR) is essential for MAPK-extracellular signal-regulated kinase (ERK)1 2 (MEK)-eukaryotic-like protein kinase (Elk) signaling and has been identified as the cytoplasm-nuclear heme transporter of ERK1 2 and hematin, the key components of stress-responsive gene expression.

Neuritin 1 (NRN1) is a member of the neuritin family. Neuritin is a glycosylphosphatidylinositol-anchored protein induced by neural activity. It is expressed in postmitotic-differentiating neurons of the developing nervous system and a population of small-diameter neurons in the dorsal root ganglia and was anterogradely and retrogradely transported. Neuritin message is induced by neuronal activity and by the activity-regulated neurotrophins BDNF, nerve growth factor (NGF), and NT-3. Purified recombinant neuritin promotes neurite outgrowth and arborization in primary embryonic hippocampal and cortical cultures. Thus, neuritin is considered as a downstream effector of activity-induced neurite outgrowth. In clinical, neuritin levels in diabetes were reduced in both dorsal root ganglia and sciatic nerve of rats, and these deficits were reversed in vivo by treatment with NGF. This manipulation of neuritin levels in diabetes may provide a potential target for therapeutic intervention in the management of neuropathy.

GADD45G, also known as CR6, is part of the nuclear proteins to interact with various proteins whose transcript levels are raised after stressful growth arrest conditions and treatment with DNA-damaging agents. GADD45G reacts to environmental stresses by mediating activation of the p38 JNK pathway which is mediated through their protein binding and activating MTK1 MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. GADD45G acts as a new-age tumor suppressor however is being frequently inactivated epigenetically in multiple tumors. GADD45G mRNA expression is down-regulated in hepatocellular carcinoma. GADD45G causes cell cycle arrest at G2 M transition when transfected into Hep-G2 cells. GADD45G induction by androgens involves new protein synthesis. Overexpression of GADD45G inhibits cell growth and causes morphological modifications in prostate cell lines thus GADD45G takes part in differentiation induction by androgens.