signalling

ECSIT is an adapter protein of the toll-like and IL-1 receptor signaling pathway that is involved in the activation of NF-kappa-B via MAP3K1. Activation of NF-kappaB as a consequence of signaling through the Toll and IL-1 receptors is a major element of innate immune responses. ECSIT is specific for the Toll IL-1 pathways and is a regulator of MEKK-1 processing. It bridges TRAF6 to MEKK-1. Expression of wild-type ECSIT accelerates processing of MEKK-1, whereas a dominant-negative fragment of ECSIT blocks MEKK-1 processing and activation of NF-kappaB. ECSIT is also required for normal embryonic development and efficient assembly of mitochondrial NADH:ubiquinone oxidoreductase.

Hippocalcin-Like Protein 1 (HPCAL1) is a neuron-specific calcium-binding member of the recoverin family which found in the retina and brain. HPCAL1 contains four EF-hand domains and it is highly similar to human hippocalcin protein. HPCAL1 is involved in the calcium-dependent regulation of rhodopsin phosphorylation. In addition, it may be of relevance for neuronal signalling in the central nervous system.

Galectin 1 (Gal-1), a β-galactoside binding mammalian lectin of 14KDa, is implicated in many signalling pathways, immune responses associated with cancer progression and immune disorders. Inhibition of human Gal-1 has been regarded as one of the potential therapeutic approaches for the treatment of cancer, as it plays a major role in tumour development and metastasis by modulating various biological functions viz. apoptosis, angiogenesis, migration, cell immune escape.

CA9 is a member of the carbonic anhydrases' family, that is often expressed in cancer cells under hypoxic condition. CA9 expression potentially contributes to the regulation of cancer cell differentiation and mediates tumour-associated genes and signalling pathways, including apoptosis, hypoxia, G2M checkpoint, PI3K AKR mTOR signalling and TGF-beta signalling pathways. CA9 Carbonic Anhydrase IX Protein, Human, Recombinant (His & Avi) is expressed in HEK293 mammalian cells with C-His-Avi tag. The predicted molecular weight is 43.7 kDa and the accession number is Q16790.

Platelet-derived growth factor receptor (PDGFR) signaling is involved in proliferation and survival in a wide array of cell types.PDGFR-β signalling, via TGF-β signalling, may be crucial for restoration of BBB integrity after cerebral ischemia and therefore represents a novel potential therapeutic target.

CA9 is a member of the carbonic anhydrases' family, that is often expressed in cancer cells under hypoxic condition. CA9 expression potentially contributes to the regulation of cancer cell differentiation and mediates tumour-associated genes and signalling pathways, including apoptosis, hypoxia, G2M checkpoint, PI3K AKR mTOR signalling and TGF-beta signalling pathways. CA9 Carbonic Anhydrase IX Protein, Cynomolgus, Recombinant (His) is expressed in HEK293 mammalian cells with C-His tag. The predicted molecular weight is 41.03 kDa and the accession number is A0A2K5VQG9.

SMAD3 belongs to the SMAD family. Members of this family mediate signal transduction by the TGF-beta activin BMP-2 4 cytokine superfamily from receptor Ser Thr protein kinases at the cell surface to the nucleus. SMAD3 is involved in cell signalling. It modulates signals of activin and TGFβ's. Binding of SMAD3 with SMAD4 enables its transmigration into the nucleus where it forms complexes with other proteins and acts as a transcription factor. SMAD3 is a receptor-regulated SMAD (R-SMAD). In mice, mutation of SMAD3 has been linked to colorectal adenocarcinoma, increased systemic inflammation, and accelerated wound healing. Increased SMAD3 activity has been implicated in the pathogenesis of scleroderma. Smad3 is also a multifaceted regulator in adipose physiology and the pathogenesis of obesity and type 2 diabetes.

Chondroitin sulphate (CS) glycosaminoglycan chains on cell and extracellular matrix proteoglycans (PGs) can no longer be regarded as merely hydrodynamic space fillers. Overwhelming evidence over recent years indicates that sulphation motif sequences within the CS chain structure are a source of significant biological information to cells and their surrounding environment. CS sulphation motifs have been shown to interact with a wide variety of bioactive molecules, e.g. cytokines, growth factors, chemokines, morphogenetic proteins, enzymes and enzyme inhibitors, as well as structural components within the extracellular milieu. They are therefore capable of modulating a panoply of signalling pathways, thus controlling diverse cellular behaviours including proliferation, differentiation, migration and matrix synthesis. Chondroitin sulfate (CS) is a sulfated glycosaminoglycan composed of a long chain of repeating disaccharide units that are attached to core proteins, resulting in CS proteoglycans (CSPGs). In the mature brain, CS is concentrated in perineuronal nets (PNNs), which are extracellular structures that surround synapses and regulate synaptic plasticity. In addition, CS is rapidly synthesized after CNS injury to create a physical and chemical barrier that inhibits axon growth.

Protein-glutamine gamma-glutamyltransferase 2, also known as Tissue transglutaminase, Transglutaminase C, Transglutaminase-2, and TGM2, is a member of the transglutaminase superfamily. TGM2 plays a role in cell growth and survival through the anti-apoptosis signaling pathway. It is a calcium-dependent acyltransferase that also undergoes a GTP-binding GTPase cycle even though it lacks any obvious sequence similarity with canonical GTP-binding (G) proteins. TGM2 is a multi-functional protein which catalyzes transamidation reactions or acts as a G-protein in intracellular signalling. As an enzyme which is responsible for the majority of transglutaminase (TG) activity in the brain, TGM2 is likely to play a modulatory role in nervous system development and has regulatory effect on neuronal cell death as well. Most importantly, numerous studies have presented data demonstrating that dysregulation of TGM2 may contribute to the pathogenesis of many neurodegenerative disorders, including Huntington's disease, Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis as well as nervous system injuries.

The type 1 IGF receptor (IGF1R) is a transmembrane tyrosine kinase that is frequently overexpressed by tumours, and mediates proliferation and apoptosis protection. IGF signalling also influences hypoxia signalling, protease secretion, tumour cell motility and adhesion, and thus can affect the propensity for invasion and metastasis. Therefore, the IGF1R is now an attractive anti-cancer treatment target. IGF1R CD221 Protein, Human, Recombinant (His & Avi) is expressed in HEK293 mammalian cells with C-His-Avi tag. The predicted molecular weight is 105.8 kDa (alpha subunit) and 23 kDa (beta subunit) and the accession number is P08069.

Follistatin-like 3 (FSTL3) is a novel cytokine that regulates insulin sensitivity and counteracts activin myostatin signalling. In the present study, regulation of FSTL3 in renal dysfunction was investigated in both human chronic kidney disease (CKD) and acute kidney dysfunction (AKD). Furthermore, mFSTL3 expression was analysed in insulin-sensitive tissues in a mouse model of CKD.

The type 1 IGF receptor (IGF1R) is a transmembrane tyrosine kinase that is frequently overexpressed by tumours, and mediates proliferation and apoptosis protection. IGF signalling also influences hypoxia signalling, protease secretion, tumour cell motility and adhesion, and thus can affect the propensity for invasion and metastasis. Therefore, the IGF1R is now an attractive anti-cancer treatment target. IGF1R CD221 Protein, Cynomolgus, Recombinant (His) is expressed in HEK293 mammalian cells with C-His tag. The predicted molecular weight is 80.59 kDa (alpha subunit) and 19.28 kDa (beta subunit) and the accession number is G7P9I7.

Integrin α-5 belongs to the Integrin α chain family and contains 7 FG-GAP repeats. Integrin α-5 joins with Integrin-β1 to form a fibronectin and laminin receptor which recognizes the sequence R-G-D in its ligands. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. It is expressed on fibroblasts, endothelial cells, peripheral T cells and platelets. Integrin α-5 undergoes post-translational cleavage in the extracellular domain to yield disulfide-linked light and heavy chains. In addition to adhesion, ITGA5 participates in cell-surface mediated signalling.

Ankyrin repeat and SOCS box protein 13(ASB13) is a member of the ankyrin repeat and SOCS box-containing (ASB) family. ASB13 contain six ankyrin repeats sequence and a SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. ASB13 may be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

May play a role in signalling in oligodendrocytes in the early stages of their terminal differentiation into myelin-forming glia and may also function in stabilizing the mature sheath. Tetraspanin-2 TSPAN2 Protein, Human, Recombinant is expressed in E. coli expression system. The predicted molecular weight is 8.8 kDa and the accession number is O60636.

Blood vessel epicardial substance (BVES), or POPDC1, is a tight junction-associated transmembrane protein that modulates epithelial-to-mesenchymal transition (EMT) via junctional signaling pathways. BVES plays a protective role both in ulcerative and infectious colitis and identify BVES as a critical protector of colonic mucosal integrity. The Popeye domain containing1, also called Bves (Popdc1 Bves), is a transmembrane protein that functions in muscle regeneration, heart rate regulation, hypoxia tolerance, and ischemia preconditioning. The expression of Popdc1 Bves is elevated in cardiomyocytes maintained in serum free defined medium. Popdc1 Bves plays a role in the preservation of cardiomyocyte viability under serum deficiency through the alteration of Rac1 activity and the regulation of Bnip3 expression by FoxO3 and NFκB transcription factors pointing to Popdc1 Bves as a potential target to enhance heart protection. Blood vessel epicardial substance (BVES) is a tight junction-associated protein that regulates epithelial-mesenchymal states and is underexpressed in epithelial malignancy. Loss of BVES promotes inflammatory tumourigenesis through dysregulation of Wnt signalling and the oncogene c-Myc. BVES promoter methylation status may serve as a CAC biomarker. Blood vessel epicardial substance (BVES Popdc1) is a junctional-associated transmembrane protein that is underexpressed in a number of malignancies and regulates epithelial-to-mesenchymal transition. BVES is a key regulator of intestinal stem cell programs and mucosal homeostasis.

Protein arginine methyltransferase 3, also known as PRMT3, is one of four type I protein arginine methyltransferases (PRMT) that in humans is encoded by the PRMT3 gene. Methylation of arginine residues is a widespread post-translational modification of proteins catalyzed by a small family of PRMTs. The modification appears to regulate protein functions and interactions that affect gene regulation, signalling and subcellular localization of proteins and nucleic acids. In human cells, the PRMT family consists of eight canonical members. PRMTs have been classified into two groups based on the end product. Certain PRMTs display different subcellular localization in different cell types, implicating cell- and tissue-specific mechanisms for regulating PRMT functions. PRMT3 is unique in that its N-terminus harbours a C2H2 zinc-finger domain that is proposed to confer substrate specificity. Besides, PRMT3 is the only type I enzyme that is restricted to the cytoplasm. A large proportion of this cystosolic PRMT3 is found associated with ribosomes. It is tethered to the ribosomes through its interaction with rpS2, which is also its substrate.

Death domain-containing protein CRADD, also known as Caspase and RIP adapter with death domain, RIP-associated protein with a death domain, CRADD and RAIDD, is a protein which is constitutively expressed in most tissues, with particularly high expression in adult heart, testis, liver, skeletal muscle, fetal liver and kidney. CRADD RAIDD contains oneCARD domain and onedeath domain. CRADD RAIDD contains a death domain involved in the binding of RIP protein. The CARD domain mediates the interaction with caspase-2. FADD MORT1 is a death domain (DD)-containing adaptor signaling molecule that interacts with the intracellular DD of FAS APO-I ( CD95 ) and tumor necrosis factor receptor 1 and the prodomain of caspase-8 ( Mch5 MACH FLICE). CRADD RAIDD has a dual-domain structure similar to that of FADD. CRADD RAIDD has an NH2-terminal caspase homology domain that interacts with caspase-2 and a COOH-terminal DD that interacts with RIP. CRADD RAIDD could play a role in regulating apoptosis in mammalian cells. CRADD RAIDD is a apoptotic adaptor molecule specific for caspase-2 and FASL TNF receptor-interacting protein RIP. In the presence of RIP and TRADD, CRADD RAIDD recruits caspase-2 to the TNFR-1 signalling complex.

RNF43 mutations are frequently detected in colorectal cancer cells and lead to a loss of function of the ubiquitin E3 ligase. The outer mitochondrial membrane 34 (TOMM34) and ring finger protein 43 (RNF43) as highly expressed oncogenes in malignant colorectal tumors. RNF43 is a tumour suppressor gene that suppresses the Wnt-beta-catenin signalling pathway. RNF43 Protein, Human, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 20.5 kDa and the accession number is Q68DV7-1.

Zika virus NS1 antigen is one of seven non-structural proteins. NS1 is involved in RNA replication. The possible effects of NS1 on hosts include: localizes to host cell surface and secreted extracellularly, modulates signalling of the innate immune system, has possible damages to platelets and endothelial cells through anti-NS1 antibodies.

ERBB2 belongs to the protein kinase superfamily, Tyr protein kinase family and EGF receptor subfamily. It contains a protein kinase domain. ERBB2 is widely expressed in epithelial cells, and amplification and or overexpression of ErbB2 has been reported associated with malignancy and a poor prognosis in numerous carcinomas, including breast, prostate and ovarian cancers. Rat ERBB2 is an essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. ErbB2 mediates signalling pathways which involve mitogen-activated protein kinase and phosphatidylinositol-3 kinase, this receptor plays a key role in development, cell proliferation and differentiation.

Human DUSP3 belongs to the dual specificity protein phosphatase subfamily. DUSPs are a heterogeneous group of protein phosphatases that can dephosphorylate both phosphotyrosine and phosphoserine phosphothreonine residues within the one substrate. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine threonine and phosphotyrosine residues. DUSPs are major modulators of critical signalling pathways that are dysregulated in various diseases. They negatively regulate members of the mitogen-activated protein kinase superfamily, which are associated with cellular proliferation and differentiation. DUSP3 is expressed in human tissues including breast and ovarian.DUSP3 shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines. Human DUSP3 specifically dephosphorylates and inactivates ERK1 and ERK2.

Mucins are key components of the mucosal barrier in the stomach that protects epithelia from carcinogenic effects of chronic inflammation. Analysis of The Cancer Genome Atlas database indicated that mucin17 (MUC17) was more highly expressed in gastric cancer (GC) specimens, with favourable prognosis for patients. And that p38 signalling is a key factor involved in MUC17-mediated inhibition of GC cell proliferation and protection against inflammatory stimulation, MUC17 upregulates the expression of MYH9 and p53, and activates the p38 pathway in GC cells through RhoA signalling.

The type 1 IGF receptor (IGF1R) is a transmembrane tyrosine kinase that is frequently overexpressed by tumours, and mediates proliferation and apoptosis protection. IGF signalling also influences hypoxia signalling, protease secretion, tumour cell motility and adhesion, and thus can affect the propensity for invasion and metastasis. Therefore, the IGF1R is now an attractive anti-cancer treatment target. IGF1R CD221 Protein, Human, Recombinant (aa 31-932, His & Avi), Biotinylated is expressed in HEK293 mammalian cells with C-His-Avi tag. The predicted molecular weight is 105.8 kDa (alpha subunit) and 23 kDa (beta subunit) and the accession number is P08069.

Tumour necrosis factor alpha (TNF-α) is a pleiotropic cytokine with both injurious and protective functions, which are thought to diverge at the level of its two cell surface receptors, TNFR1 and TNFR2. In the setting of acute injury, selective inhibition of TNFR1 is predicted to attenuate the cell death and inflammation associated with TNF-α, while sparing or potentiating the protective effects of TNFR2 signalling.

CD82, also known as KAI-1, structurally belongs to tetraspanin family while categorised as metastasis suppressor gene on functional grounds. KAI1 CD82 is localized on cell membrane and form interactions with other tetraspanins, integrins and chemokines which are respectively responsible for cell migration, adhesion and signalling. Downregulation of CD82 expression is associated with the advanced stages of many human cancers and correlates with the acquisition of metastatic potential. Recent studies suggest that complex mechanisms underlie CD82 loss of function, including altered transcriptional regulation, splice variant production and post-translational protein modifications, and indicate a central role for CD82 in controlling metastasis as a 'molecular facilitator'. The loss of KAI1 CD82 expression in invasive and metastatic cancers is due to a complex, epigenetic mechanism that probably involves transcription factors such as NFkappaB, p53, and beta-catenin. A loss of KAI1 expression is also associated with the advanced stages of many human malignancies and results in the acquisition of invasive and metastatic capabilities by tumour cells. Thus, KAI1 CD82 is regarded as a wide-spectrum tumor metastasis suppressor.

Tribbles homolog 2, also known as TRB-2, and Trib2, is a member of the protein kinase superfamily and Tribbles subfamily (Trib1, Trib2, Trib3). The identification of tribbles as regulators of signal processing systems and physiological processes, including development, together with their potential involvement in diabetes and cancer, has generated considerable interest in these proteins. Tribbles have been reported to regulate the activation of some intracellular signalling pathways with roles extending from mitosis and cell activation to apoptosis and modulation of gene expression. Tribbles control the timing of mitosis in the prospective mesoderm, allowing cell-shape changes to be completed. This mechanism for coordinating cell division and cell-shape changes may have helped Drosophila to evolve its mode of rapid early development. Trib2 was identified as a downregulated transcript in leukemic cells undergoing growth arrest. Trib2-transduced bone marrow cells exhibited a growth advantage and readily established factor-dependent cell lines. Trib2-reconstituted mice uniformly developed fatal transplantable acute myelogenous leukemia (AML).

Serine threonine-protein kinase 16, also known as myristoylated and palmitoylated serine threonine-protein kinase, Protein kinase PKL12, TGF-beta-stimulated factor 1, TSF-1, MPSK1 and STK16, is a membrane protein that is ubiquitously expressed at very low levels. STK16 MPSK1 belongs to the protein kinase superfamily and Ser Thr protein kinase family. It contains one protein kinase domain. Transforming growth factor-beta (TGF-beta) shows a variety of biological activities in various organs or cells. Some factors such as Smads (Sma and Mad proteins) and TGF-beta activating kinase 1 have been characterized as signalling molecules downstream of TGF-beta. Several TGF-beta response elements have been identified such as cAMP response element, Smad binding element, and recognition sites for activating protein-1 and stimulating protein-1 in various gene promoters. STK16 MPSK1 is a unique factor with two biological functions, transcriptional regulation and protein phosphorylation, that may be involved in TGF-beta signals. STK16 MPSK1 is a protein kinase that acts on both serine and threonine residues. STK16 MPSK1 possessed DNA-binding ability and activated the TGF-beta responsive CNP promoter or vascular endothelial growth factor gene promoter which possesses a sequence element analogous to the TGF-beta responsive GC-rich element of the CNP promoter. STK16 MPSK1 did not directly activate a Smads-dependent promoter from plasminogen activator inhibitor 1 gene, but it showed enhancement in co-operation with Smad3 and Smad4. STK16 MPSK1 mRNA as well as its protein level were stimulated by TGF-beta treatment.

Amphiregulin (AREG) is a member of the epidermal growth factor (EGF) family and is expressed in a plethora of cancers. Tumour growth and metastasis were decreased by AREG silencing in an orthotopic model of pancreatic cancer. AREG may play a critical role in cell migration, invasion, and EMT by activating the EGFR ERK NF‑κB signalling pathway in pancreatic cancer cells.

Galectin 1(Gal-1), a β-galactoside binding mammalian lectin of 14KDa, is implicated in many signalling pathways, immune responses associated with cancer progression and immune disorders. Inhibition of human Gal-1 has been regarded as one of the potential therapeutic approaches for the treatment of cancer, as it plays a major role in tumour development and metastasis by modulating various biological functions viz. apoptosis, angiogenesis, migration, cell immune escape.

A natural soluble form of CD21 that is cleaved from lymphocyte membrane CD21 circulates in normal human serum. Soluble CD21 retains the capacity to bind iC3b and CD23, the known ligands of membrane CD21. In a similar fashion to IgE complexes, another ligand of CD23, the soluble CD21 was shown to efficiently trigger CD23-signalling pathways in human monocytes.

Lrrn1 is required for the formation of MHB--loss of function leads to a loss of the morphological constriction and loss of Fgf8. Cells overexpressing Lrrn1 violate the boundary and result in a loss of cell restriction between midbrain and hindbrain compartments. Lrrn1 also regulates the glycosyltransferase Lunatic Fringe, a modulator of Notch signalling, maintaining its expression in midbrain cells which is instrumental in MHB boundary formation.

The three fibronectin leucine-rich repeat transmembrane (FLRT) proteins contain 10 leucine-rich repeats (LRR), a type III fibronectin (FN) domain, followed by the transmembrane region, and a short cytoplasmic tail. FLRT1 is expressed in kidney and brain, which is a target for tyrosine phosphorylation mediated by FGFR1 and implicates a non-receptor Src family kinase (SFK). All FLRTs can interact with FGFR1 and FLRTs can be induced by the activation of FGF signalling by FGF-2. The phosphorylation state of FLRT1, which is itself FGFR1 dependent, may play a critical role in the potentiation of FGFR1 signalling and may also depend on a SFK-dependent phosphorylation mechanism acting via the FGFR. This is consistent with an 'in vivo' role for FLRT1 regulation of FGF signalling via SFKs. Furthermore, the phosphorylation-dependent futile cycle mechanism controlling FGFR1 signalling is concurrently crucial for regulation of FLRT1-mediated neurite outgrowth. FLRT1, FLRT2 and FLRT3 are members of the fibronectin leucine rich transmembrane protein (FLRT) family. They may function in cell adhesion and or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular matrix. FLRT3 shares 55% amino acid sequence identity with FLRT1.

Leucine-rich repeat transmembrane protein FLRT3, also known as Fibronectin-like domain-containing leucine-rich transmembrane protein 3, and FLRT3, is a single-pass type I membrane protein which belongs to the fibronectin leucine rich transmembrane protein (FLRT) family. FLRT3 contains one fibronectin type-III domain and ten LRR (leucine-rich) repeats and is expressed in kidney, brain, pancreas, skeletal muscle, lung, liver, placenta, and heart. It has a provocative expression pattern during somite development being expressed in regions of the somite where muscle precursor cells migrate from the dermomyotome and move into the myotome, and later in myotomal precursors destined to migrate towards their final destination. FLRT1, FLRT2 and FLRT3 are members of the FLRT family. The FLRT family of leucine-rich repeat (LRR) proteins is implicated in fibroblast growth factor (FGF) signalling, early embryonic development and neurite outgrowth. FLRT3 shares 55% amino acid sequence identity with FLRT1 and 44% identity with FLRT2. Two alternatively spliced transcript variants encoding the same protein have been described. The expression of FLRT3 is controlled by fibroblast growth factors (FGFs). FLRT3 has been implicated in neurite outgrowth after nerve damage, as a positive regulator of FGF signalling and in homotypic cell adhesion. FLRT3 may have a crucial role in regulating cellular adhesion between the epithelial apical ridge and the underlying mesenchyme and in establishing the dorso-ventral position of the ridge.

TWSG1 belongs to the twisted gastrulation protein family. TWSG1 from different species are functionally equivalent. In contrast to Drosophila where TWSG1 expression is limited to early embryos, expression of TWSG1 is found throughout mouse and human development. Mutations in the TWSG1 gene cause at least some of the cells on the dorsal half of the embryo to adopt more ventral cell fates. This is thought to involve gradients of the signaling molecule decapentaplegic. TWSG1 may function as a bone morphogenetic protein signalling agonist or antagonize these activities. It can dislodge latent bone morphogenetic proteins and thus provides a permissive signal that allows high BMP signaling in the embryo. TWSG1 is a cofactor in the antagonism of chordin to BMP signaling. It also binds both the vertebrate Decapentaplegic ortholog BMP4 and chordin and forms ternary complexes. Meanwhile, TWSG1 increases binding of chordin to BMP4, potentiates the ability of chordin to induce secondary axes in Xenopus embryos, and enhances chordin cleavage by vertebrate proteases related to tolloid at a site poorly used in the absence of TWSG1. The presence of TWSG1 enhances the secondary axis-inducing activity of 2 products of chordin cleavage.

FGF (fibroblast growth factor) signalling is known to be required for many aspects of mesoderm formation and patterning during Xenopus development and has been implicated in regulating genes required for the specification of both blood and skeletal muscle lineages. Fibroblast growth factor 4 (FGF4) signaling induces differentiation from embryonic stem cells (ESCs) via the phosphorylation of downstream molecules such as mitogen-activated protein kinase extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1 2 (ERK1 2). Fibroblast Growth Factor 4 (FGF-4) could not only increase the proliferation of bone marrow mesenchymal stem cells (BMSCs), but also induce BMSCs into hepatocyte-like cells in vitro. FGF4 transduced BMSCs contributed to liver regeneration might by the transplanted microenvironment. The FGF4-bFGF BMSCs thus can enhance the survival of the transplanted cells, diminish myocardial fibrosis, promote myocardial angiogenesis, and improve cardiac functions.

NOV, also called CCN3, is a secreted protein of CCN family members. CCN family members are highly conserved cysteine rich proteins sharing a common modular structure having 4 conserved domains, insulin-like growth factor-binding protein (IGFBP) domain, von Willebrand type C (VWC) domain, thrombospondin-1 (TSP-1) domain, and C-terminal (CT) domain (absent in CCN5). By specific interactions with these domains, CCN proteins modulate multiple signalling pathways including BMPs, Wnt, TGFs, Notch and integrins to regulate cell proliferation, differentiation, adhesion, migration, angiogenesis, and survival. CCN3 is firstly characterized as a promoter of progenitor activity of human hematopoietic stem cells, as knockdown of CCN3 can abrogate the function of primitive progenitors. Recent studies showed that CCN3 is also actively involved in the process of wound healing. CCN3 is highly expressed in granulation tissues of cutaneous wounds and capable of inducing synthetic responses of fibroblasts.

Mucin-15 is a single-pass type I membrane protein member of the Mucin family. Mucins are a family of high molecular weight, heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues in most metazoans. A key characteristic of Mucins is their ability to form gels. Therefore they are a key component in most gel-like secretions, serving functions from lubrication to cell signalling to forming chemical barriers. Mucin-15 is expressed in many tissues. Mucin-15 is highly glycosylated (N- and O-linked carbohydrates). Mucin-15 may play a role in the cell adhesion to the extracellular matrix.

RGS5 is a member of the RGS superfamily and acts as a negative regulator of heterotrimeric G protein-mediated signalling through G protein-coupled receptors (GPCRs). The regulator of G-protein signaling (RGS) proteins have recently been identified as signal transduction molecules which have structural homology to SST2 of Saccharomyces cerevisiae and EGL-10 of Caenorhabditis elegans. The messenger RNA of hRGS5 was abundantly expressed in heart, lung, skeletal muscle, and small intestine, and at low levels in brain, placenta, liver, colon, and leukocytes.

RNF43 mutations are frequently detected in colorectal cancer cells and lead to a loss of function of the ubiquitin E3 ligase. The outer mitochondrial membrane 34 (TOMM34) and ring finger protein 43 (RNF43) as highly expressed oncogenes in malignant colorectal tumors. RNF43 is a tumour suppressor gene that suppresses the Wnt-beta-catenin signalling pathway. RNF43 Protein, Human, Recombinant (hFc) is expressed in HEK293 mammalian cells with hFc tag. The predicted molecular weight is 45.8 kDa and the accession number is Q68DV7-1.

G-protein coupled receptor kinase 2 (GRK2), also referred as Adrenergic, beta, receptor kinase 1 (ADRBK1), is a ubiquitous member of the G protein-coupled receptor kinase (GRK) family that appears to play a central, integrative role in signal transduction cascades. GRK2 can phosphorylate a growing number of non-GPCR substrates and associate with a variety of proteins related to signal transduction, thus suggesting that this kinase could also have diverse 'effector' functions. GRK2 has been reported to interact with a variety of signal transduction proteins related to cell migration such as MEK, Akt, PI3Kgamma or GIT. Interestingly, the levels of expression and activity of this kinase are altered in a number of inflammatory disorders (as rheumatoid arthritis or multiple sclerosis), thus suggesting that GRK2 may play an important role in the onset or development of these pathologies. The important physiological function of GRK2 as a modulator of the efficacy of GPCR signal transduction systems is exemplified by its relevance in cardiovascular physiopathology as well as by its emerging role in the regulation of chemokine receptors. Besides its canonical role in the modulation of the signalling mediated by many G protein-coupled receptors (GPCR), this protein can display a very complex network of functional interactions with a variety of signal transduction partners, in a stimulus, cell type, or context-specific way.

Oxidative stress-responsive 1 protein (OXSR1), also known as Serine threonine-protein kinase OSR1, is a member of the Ser Thr protein kinase family of proteins. OXSR1 regulates downstream kinases in response to environmental stress, and may play a role in regulating the actin cytoskeleton. OXSR1 is a 58 kDa protein of 527 amino acids that is widely expressed in mammalian tissues and cell lines. The amino acid (aa) sequence of the predicted OXSR1 protein is 39% identical to that of human SOK1. Of potential regulators surveyed, endogenous OXSR1 is activated only by osmotic stresses, notably sorbitol and to a lesser extent NaCl. OXSR1 did not increase the activity of coexpressed JNK, nor did it activate three other MAPKs, p38, ERK2, and ERK5. Phosphorylation by OXSR1 modulates the G protein sensitivity of PAK isoforms. The OXSR1 and SPAK are key enzymes in a signalling cascade regulating the activity of Na+ K+ 2Cl- co-transporters (NKCCs) in response to osmotic stress. Both kinases have a conserved carboxy-terminal (CCT) domain, which recognizes a unique peptide (Arg-Phe-Xaa-Val) motif. The OXSR1 and SPAK kinases specifically recognize their upstream activators and downstream substrates.