Activin Receptors, Type II: One of the two types of ACTIVIN RECEPTORS. They are membrane protein kinases belonging to the family of PROTEIN-SERINE-THREONINE KINASES. The major type II activin receptors are ActR-IIA and ActR-IIB.Activin Receptors: Receptors for ACTIVINS are membrane protein kinases belonging to the family of PROTEIN-SERINE-THREONINE KINASES, thus also named activin receptor-like kinases (ALK's). Activin receptors also bind TRANSFORMING GROWTH FACTOR BETA. As those transmembrane receptors of the TGF-beta superfamily (RECEPTORS, TRANSFORMING GROWTH FACTOR BETA), ALK's consist of two different but related protein kinases, Type I and Type II. Activins initiate cellular signal transduction by first binding to the type II receptors (ACTIVIN RECEPTORS, TYPE II ) which then recruit and phosphorylate the type I receptors (ACTIVIN RECEPTORS, TYPE I ) with subsequent activation of the type I kinase activity.Activins: Activins are produced in the pituitary, gonads, and other tissues. By acting locally, they stimulate pituitary FSH secretion and have diverse effects on cell differentiation and embryonic development. Activins are glycoproteins that are hetero- or homodimers of INHIBIN-BETA SUBUNITS.Activin Receptors, Type I: One of the two types of ACTIVIN RECEPTORS or activin receptor-like kinases (ALK'S). There are several type I activin receptors. The major active ones are ALK-2 (ActR-IA) and ALK-4 (ActR-IB).Myostatin: A growth differentiation factor that is a potent inhibitor of SKELETAL MUSCLE growth. It may play a role in the regulation of MYOGENESIS and in muscle maintenance during adulthood.Inhibins: Glycoproteins that inhibit pituitary FOLLICLE STIMULATING HORMONE secretion. Inhibins are secreted by the Sertoli cells of the testes, the granulosa cells of the ovarian follicles, the placenta, and other tissues. Inhibins and ACTIVINS are modulators of FOLLICLE STIMULATING HORMONE secretions; both groups belong to the TGF-beta superfamily, as the TRANSFORMING GROWTH FACTOR BETA. Inhibins consist of a disulfide-linked heterodimer with a unique alpha linked to either a beta A or a beta B subunit to form inhibin A or inhibin B, respectivelyInhibin-beta Subunits: They are glycopeptides and subunits in INHIBINS and ACTIVINS. Inhibins and activins belong to the transforming growth factor beta superfamily.Follistatin: A broadly distributed protein that binds directly to ACTIVINS. It functions as an activin antagonist, inhibits FOLLICLE STIMULATING HORMONE secretion, regulates CELL DIFFERENTIATION, and plays an important role in embryogenesis. Follistatin is a single glycosylated polypeptide chain of approximately 37-kDa and is not a member of the inhibin family (INHIBINS). Follistatin also binds and neutralizes many members of the TRANSFORMING GROWTH FACTOR BETA family.Receptors, Interleukin-1 Type I: An interleukin-1 receptor subtype that is involved in signaling cellular responses to INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The binding of this receptor to its ligand causes its favorable interaction with INTERLEUKIN-1 RECEPTOR ACCESSORY PROTEIN and the formation of an activated receptor complex.Receptors, Transforming Growth Factor beta: Cell-surface proteins that bind transforming growth factor beta and trigger changes influencing the behavior of cells. Two types of transforming growth factor receptors have been recognized. They differ in affinity for different members of the transforming growth factor beta family and in cellular mechanisms of action.Receptors, Growth Factor: Cell surface receptors that bind growth or trophic factors with high affinity, triggering intracellular responses which influence the growth, differentiation, or survival of cells.Smad2 Protein: A receptor-regulated smad protein that undergoes PHOSPHORYLATION by ACTIVIN RECEPTORS, TYPE I. It regulates TRANSFORMING GROWTH FACTOR BETA and ACTIVIN signaling.Receptors, Interleukin-1: Cell surface receptors that are specific for INTERLEUKIN-1. Included under this heading are signaling receptors, non-signaling receptors and accessory proteins required for receptor signaling. Signaling from interleukin-1 receptors occurs via interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88.Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Receptors, Tumor Necrosis Factor, Type I: A tumor necrosis factor receptor subtype that has specificity for TUMOR NECROSIS FACTOR ALPHA and LYMPHOTOXIN ALPHA. It is constitutively expressed in most tissues and is a key mediator of tumor necrosis factor signaling in the vast majority of cells. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Receptors, Interleukin-1 Type II: An interleukin-1 receptor subtype that competes with the INTERLEUKIN-1 RECEPTOR TYPE I for binding to INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The interleukin-1 type II receptor appears to lack signal transduction capability. Therefore it may act as a "decoy" receptor that modulates the activity of its ligands. Both membrane-bound and soluble forms of the receptor have been identified.Nodal Protein: The founding member of the nodal signaling ligand family of proteins. Nodal protein was originally discovered in the region of the mouse embryo primitive streak referred to as HENSEN'S NODE. It is expressed asymmetrically on the left side in chordates and plays a critical role in the genesis of left-right asymmetry during vertebrate development.Bone Morphogenetic Proteins: Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins.Interleukin-1 Receptor Accessory Protein: A protein that takes part in the formation of active interleukin-1 receptor complex. It binds specifically to INTERLEUKIN-1 and the INTERLEUKIN-1 RECEPTOR TYPE I at the cell surface to form a heterotrimeric complex that brings its cytoplasmic domain into contact with the cytoplasm domain of the TYPE-I INTERLEUKIN-1 RECEPTOR. Activation of intracellular signal transduction pathways from the receptor is believed to be driven by this form of cytoplasmic interaction.Smad Proteins: A family of proteins that are involved in the translocation of signals from TGF-BETA RECEPTORS; BONE MORPHOGENETIC PROTEIN RECEPTORS; and other surface receptors to the CELL NUCLEUS. They were originally identified as a class of proteins that are related to the mothers against decapentaplegic protein, Drosophila and sma proteins from CAENORHABDITIS ELEGANS.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Interleukin-1: A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Interleukin 1 Receptor Antagonist Protein: A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA.Mink: Carnivores of genus Mustela of the family MUSTELIDAE. The European mink, which has white upper and lower lips, was widely trapped for commercial purposes and is classified as endangered. The American mink, lacking a white upper lip, is farmed commercially.Bone Morphogenetic Protein Receptors, Type I: A subtype of bone morphogenetic protein receptors with high affinity for BONE MORPHOGENETIC PROTEINS. They can interact with and undergo PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II. They signal primarily through RECEPTOR-REGULATED SMAD PROTEINS.Growth Differentiation Factors: A family of BONE MORPHOGENETIC PROTEIN-related proteins that are primarily involved in regulation of CELL DIFFERENTIATION.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Mice, Inbred C57BLBone Morphogenetic Protein Receptors, Type II: A subtype of bone morphogenetic protein receptors with low affinity for BONE MORPHOGENETIC PROTEINS. They are constitutively active PROTEIN-SERINE-THREONINE KINASES that can interact with and phosphorylate TYPE I BONE MORPHOGENETIC PROTEIN RECEPTORS.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Smad3 Protein: A receptor-regulated smad protein that undergoes PHOSPHORYLATION by ACTIVIN RECEPTORS, TYPE I. Activated Smad3 can bind directly to DNA, and it regulates TRANSFORMING GROWTH FACTOR BETA and ACTIVIN signaling.Mesoderm: The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube.Smad4 Protein: A signal transducing adaptor protein and tumor suppressor protein. It forms a complex with activated RECEPTOR-REGULATED SMAD PROTEINS. The complex then translocates to the CELL NUCLEUS and regulates GENETIC TRANSCRIPTION of target GENES.Sialoglycoproteins: Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities.Interferon Type I: Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Scavenger Receptors, Class B: A family of scavenger receptors that are predominately localized to CAVEOLAE of the PLASMA MEMBRANE and bind HIGH DENSITY LIPOPROTEINS.Growth Substances: Signal molecules that are involved in the control of cell growth and differentiation.In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Embryonic Induction: The complex processes of initiating CELL DIFFERENTIATION in the embryo. The precise regulation by cell interactions leads to diversity of cell types and specific pattern of organization (EMBRYOGENESIS).Xenopus Proteins: Proteins obtained from various species of Xenopus. Included here are proteins from the African clawed frog (XENOPUS LAEVIS). Many of these proteins have been the subject of scientific investigations in the area of MORPHOGENESIS and development.Collagen Type I: The most common form of fibrillar collagen. It is a major constituent of bone (BONE AND BONES) and SKIN and consists of a heterotrimer of two alpha1(I) and one alpha2(I) chains.Myositis Ossificans: A disease characterized by bony deposits or the ossification of muscle tissue.Receptors, Scavenger: A large group of structurally diverse cell surface receptors that mediate endocytic uptake of modified LIPOPROTEINS. Scavenger receptors are expressed by MYELOID CELLS and some ENDOTHELIAL CELLS, and were originally characterized based on their ability to bind acetylated LOW-DENSITY LIPOPROTEINS. They can also bind a variety of other polyanionic ligand. Certain scavenger receptors can internalize micro-organisms as well as apoptotic cells.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Granulosa Cells: Supporting cells for the developing female gamete in the OVARY. They are derived from the coelomic epithelial cells of the gonadal ridge. Granulosa cells form a single layer around the OOCYTE in the primordial ovarian follicle and advance to form a multilayered cumulus oophorus surrounding the OVUM in the Graafian follicle. The major functions of granulosa cells include the production of steroids and LH receptors (RECEPTORS, LH).Antigens, CD36: Leukocyte differentiation antigens and major platelet membrane glycoproteins present on MONOCYTES; ENDOTHELIAL CELLS; PLATELETS; and mammary EPITHELIAL CELLS. They play major roles in CELL ADHESION; SIGNAL TRANSDUCTION; and regulation of angiogenesis. CD36 is a receptor for THROMBOSPONDINS and can act as a scavenger receptor that recognizes and transports oxidized LIPOPROTEINS and FATTY ACIDS.

Crystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12. (1/587)

Activation of the type I TGFbeta receptor (TbetaR-I) requires phosphorylation of a regulatory segment known as the GS region, located upstream of the serine/threonine kinase domain in the cytoplasmic portion of the receptor. The crystal structure of a fragment of unphosphorylated TbetaR-I, containing both the GS region and the catalytic domain, has been determined in complex with the FK506-binding protein FKBP12. TbetaR-I adopts an inactive conformation that is maintained by the unphosphorylated GS region. FKBP12 binds to the GS region of the receptor, capping the TbetaR-II phosphorylation sites and further stabilizing the inactive conformation of TbetaR-I. Certain structural features at the catalytic center of TbetaR-I are characteristic of tyrosine kinases rather than Ser/Thr kinases.  (+info)

Transforming growth factor-beta induces formation of a dithiothreitol-resistant type I/Type II receptor complex in live cells. (2/587)

Transforming growth factor-beta (TGF-beta) binds to and signals via two serine-threonine kinase receptors, the type I (TbetaRI) and type II (TbetaRII) receptors. We have used different and complementary techniques to study the physical nature and ligand dependence of the complex formed by TbetaRI and TbetaRII. Velocity centrifugation of endogenous receptors suggests that ligand-bound TbetaRI and TbetaRII form a heteromeric complex that is most likely a heterotetramer. Antibody-mediated immunofluorescence co-patching of epitope-tagged receptors provides the first evidence in live cells that TbetaRI. TbetaRII complex formation occurs at a low but measurable degree in the absence of ligand, increasing significantly after TGF-beta binding. In addition, we demonstrate that pretreatment of cells with dithiothreitol, which inhibits the binding of TGF-beta to TbetaRI, does not prevent formation of the TbetaRI.TbetaRII complex, but increases its sensitivity to detergent and prevents TGF-beta-activated TbetaRI from phosphorylating Smad3 in vitro. This indicates that either a specific conformation of the TbetaRI. TbetaRII complex, disrupted by dithiothreitol, or direct binding of TGF-beta to TbetaRI is required for signaling.  (+info)

Interaction of 5-lipoxygenase with cellular proteins. (3/587)

5-Lipoxygenase (5LO) plays a pivotal role in cellular leukotriene synthesis. To identify proteins interacting with human 5LO, we used a two-hybrid approach to screen a human lung cDNA library. From a total of 1.5 x 10(7) yeast transformants, nine independent clones representing three different proteins were isolated and found to specifically interact with 5LO. Four 1.7- to 1.8-kb clones represented a 16-kDa protein named coactosin-like protein for its significant homology with coactosin, a protein found to be associated with actin in Dictyostelium discoideum. Coactosin-like protein thus may provide a link between 5LO and the cytoskeleton. Two other yeast clones of 1.5 kb encoded transforming growth factor (TGF) type beta receptor-I-associated protein 1 partial cDNA. TGF type beta receptor-I-associated protein 1 recently has been reported to associate with the activated form of the TGF beta receptor I and may be involved in the TGF beta-induced up-regulation of 5LO expression and activity observed in HL-60 and Mono Mac 6 cells. Finally, three identical 2.1-kb clones contained the partial cDNA of a human protein with high homology to a hypothetical helicase K12H4. 8 from Caenorhabditis elegans and consequently was named DeltaK12H4. 8 homologue. Analysis of the predicted amino acid sequence revealed the presence of a RNase III motif and a double-stranded RNA binding domain, indicative of a protein of nuclear origin. The identification of these 5LO-interacting proteins provides additional approaches to studies of the cellular functions of 5LO.  (+info)

Dominant-negative Smad2 mutants inhibit activin/Vg1 signaling and disrupt axis formation in Xenopus. (4/587)

Smads are central mediators of signal transduction for the TGFbeta superfamily. However, the precise functions of Smad-mediated signaling pathways in early development are unclear. Here we demonstrate a requirement for Smad2 signaling in dorsoanterior axis formation during Xenopus development. Using two point mutations of Smad2 previously identified in colorectal carcinomas, we show that Smad2 ushers Smad4 to the nucleus to form a transcriptional activation complex with the nuclear DNA-binding protein FAST-1 and that the mutant proteins interact normally with FAST-1 but fail to recruit Smad4 into the nucleus. This mechanism of inhibition specifically restricts the dominant-negative activity of these mutants to the activin/Vg1 signaling pathway without inhibiting BMPs. Furthermore, expression of these mutants in Xenopus animal caps inhibits but does not abolish activin and Vg1 induction of mesoderm and in the embryo results in a truncated dorsoanterior axis. These studies define a mechanism through which mutations in Smad2 may block TGFbeta-dependent signaling and suggest a critical role for inductive signaling mediated by the Smad2 pathway in Xenopus organizer function.  (+info)

A short loop on the ALK-2 and ALK-4 activin receptors regulates signaling specificity but cannot account for all their effects on early Xenopus development. (5/587)

Activin, a member of the transforming growth factor beta (TGF-beta) superfamily, signals through a heteromeric complex of type I and type II serine-threonine kinase receptors. The two activin type I receptors previously identified, ALK-2 (ActR-I) and ALK-4 (ActR-IB), have distinct effects on gene expression, differentiation and morphogenesis in the Xenopus animal cap assay. ALK-4 reproduces the effects of activin treatment including the dose-dependent induction of progressively more dorso-anterior mesodermal and endodermal markers, whereas ALK-2 induces only ventral mesodermal markers and counteracts the effects of ALK-4. To identify regions of the receptors that determine signaling specificity we have generated chimeras of the constitutively active ALK-2 and ALK-4 receptors (termed ALK-2* and ALK-4*). The effects of these chimeric receptors on gene expression and morphogenetic movements implicate the loop between kinase subdomains IV and V in mediating the strong dorsal gene-inducing properties of ALK-4*; when the seven amino acids comprising this loop are transferred from ALK-4* to ALK-2*, the resulting chimeric receptor is capable of inducing the expression of dorsal-specific genes. In contrast, when the equivalent region of ALK-2* is transferred to the ALK-4* backbone it cannot effectively counteract the dorsalizing effects of ALK-4*, suggesting that other regions of type I receptors are also involved in determining signal specificity.  (+info)

TAKs, thylakoid membrane protein kinases associated with energy transduction. (6/587)

The phosphorylation of proteins within the eukaryotic photosynthetic membrane is thought to regulate a number of photosynthetic processes in land plants and algae. Both light quality and intensity influence protein kinase activity via the levels of reductants produced by the thylakoid electron transport chain. We have isolated a family of proteins called TAKs, Arabidopsis thylakoid membrane threonine kinases that phosphorylate the light harvesting complex proteins. TAK activity is enhanced by reductant and is associated with the photosynthetic reaction center II and the cytochrome b6f complex. TAKs are encoded by a gene family that has striking similarity to transforming growth factor beta receptors of metazoans. Thus thylakoid protein phosphorylation may be regulated by a cascade of reductant-controlled membrane-bound protein kinases.  (+info)

The type I serine/threonine kinase receptor ActRIA (ALK2) is required for gastrulation of the mouse embryo. (7/587)

ActRIA (or ALK2), one of the type I receptors of the transforming growth factor-beta (TGF-beta) superfamily, can bind both activin and bone morphogenetic proteins (BMPs) in conjunction with the activin and BMP type II receptors, respectively. In mice, ActRIA is expressed primarily in the extraembryonic visceral endoderm before gastrulation and later in both embryonic and extraembryonic cells during gastrulation. To elucidate its function in mouse development, we disrupted the transmembrane domain of ActRIA by gene targeting. We showed that embryos homozygous for the mutation were arrested at the early gastrulation stage, displaying abnormal visceral endoderm morphology and severe disruption of mesoderm formation. To determine in which germ layer ActRIA functions during gastrulation, we performed reciprocal chimera analyses. (1) Homozygous mutant ES cells injected into wild-type blastocysts were able to contribute to all three definitive germ layers in chimeric embryos. However, a high contribution of mutant ES cells in chimeras disrupted normal development at the early somite stage. (2) Consistent with ActRIA expression in the extraembryonic cells, wild-type ES cells failed to rescue the gastrulation defect in chimeras in which the extraembryonic ectoderm and visceral endoderm were derived from homozygous mutant blastocysts. Furthermore, expression of HNF4, a key visceral endoderm-specific transcription regulatory factor, was significantly reduced in the mutant embryos. Together, our results indicate that ActRIA in extraembryonic cells plays a major role in early gastrulation, whereas ActRIA function is also required in embryonic tissues during later development in mice.  (+info)

Parathyroid hormone-related peptide (PTHrP)-dependent and -independent effects of transforming growth factor beta (TGF-beta) on endochondral bone formation. (8/587)

Previously, we showed that expression of a dominant-negative form of the transforming growth factor beta (TGF-beta) type II receptor in skeletal tissue resulted in increased hypertrophic differentiation in growth plate and articular chondrocytes, suggesting a role for TGF-beta in limiting terminal differentiation in vivo. Parathyroid hormone-related peptide (PTHrP) has also been demonstrated to regulate chondrocyte differentiation in vivo. Mice with targeted deletion of the PTHrP gene demonstrate increased endochondral bone formation, and misexpression of PTHrP in cartilage results in delayed bone formation due to slowed conversion of proliferative chondrocytes into hypertrophic chondrocytes. Since the development of skeletal elements requires the coordination of signals from several sources, this report tests the hypothesis that TGF-beta and PTHrP act in a common signal cascade to regulate endochondral bone formation. Mouse embryonic metatarsal bone rudiments grown in organ culture were used to demonstrate that TGF-beta inhibits several stages of endochondral bone formation, including chondrocyte proliferation, hypertrophic differentiation, and matrix mineralization. Treatment with TGF-beta1 also stimulated the expression of PTHrP mRNA. PTHrP added to cultures inhibited hypertrophic differentiation and matrix mineralization but did not affect cell proliferation. Furthermore, terminal differentiation was not inhibited by TGF-beta in metatarsal rudiments from PTHrP-null embryos; however, growth and matrix mineralization were still inhibited. The data support the model that TGF-beta acts upstream of PTHrP to regulate the rate of hypertrophic differentiation and suggest that TGF-beta has both PTHrP-dependent and PTHrP-independent effects on endochondral bone formation.  (+info)

Transforming growth factor beta1 (TGFbeta1) is a potent growth inhibitor for most cells, including neoplastic cells. However, there are several types of malignant cells that are resistant to its growth-inhibitory effect. LMC19, a highly malignant rat urothelial cell line, lacks TGFbeta1 receptor (TbetaRI) and is insensitive to the growth-suppresive effect of TGFbeta1. We transfected an expression vector containing human TbetaRI into this cell line. In control cells transfected with the neo gene alone, no inhibitory effect on growth was observed in vitro by the addition of anti-TGFbeta1 antibody or recombinant TGFbeta1 into serum-free medium. In contrast, the growth of all transfectants tested was inhibited significantly under serum-free conditions because of their endogenous TGFbeta synthesis. The growth was reduced further by the addition of recombinant TGFbeta1. This response pattern is consistent with TGFbeta1 mediating its effects by an autocrine and paracrine mechanism. The tumorigenicity ...
Plasmid pRK5 TGF beta type I receptor (T202D) Flag from Dr. Rik Deryncks lab contains the insert TGF beta type I receptor and is published in J Biol Chem. 1996 May 31. 271(22):13123-9. This plasmid is available through Addgene.
1PY5: Synthesis and activity of new aryl- and heteroaryl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain.
The TGF-β superfamily is a large family of growth and differentiation factors that regulate a wide variety of cellular processes in many different cell types and biological contexts. Different family members regulate cell proliferation (both positively and negatively), migration, extracellular matrix elaboration, adhesion, survival and differentiation, in both developing embryos and adult organisms, ranging from worms to humans (Whitman, 1998; Massagué and Chen, 2000; Massagué et al., 2000). Aberrant signaling by TGF-β, the prototype of the family, has been implicated in a number of human diseases, including cancer, hereditary hemorrhagic telangiectasia, atherosclerosis, and fibrotic disease of the kidney, liver, and lung (Blobe et al., 2000). In addition, low levels of TGF-β signaling have been implicated in compromised wound healing, and inappropriately high levels of TGF-β signaling are associated with excessive scarring (Roberts and Sporn, 1993).. The mechanism of signaling by TGF-β ...
TGF-β 3 superfamily is a group of multifunctional cytokines that affect cell growth, differentiation, apoptosis, and morphogenesis (1, 2, 3) . This family consists of ,40 family members, including TGF-βs, activins, and BMPs. TGF-β superfamily ligands induce heteromeric complex formation of cognate type II and type I serine/threonine kinase receptors. Type II receptor kinases then phosphorylate serine and threonine residues in the GS domain of type I receptors, which results in the activation of type I receptor kinases (4) . Activated type I receptors signal into cytoplasm through phosphorylation of Smad proteins. Thus far, eight mammalian Smad proteins have been identified. Smad1, Smad2, Smad3, Smad5, and Smad8 are R-Smads, which are directly phosphorylated by type I receptors. Smad2 and Smad3 are activated by the TGF-β type I receptor and the activin type IB receptor, whereas Smad1, Smad5, and Smad8 are activated by BMP type I receptors and activin receptor-like kinase 1. Smad4 is a Co-Smad ...
This gene encodes a type I cell-surface receptor for the TGF-beta superfamily of ligands. It shares with other type I receptors a high degree of similarity in serine-threonine kinase subdomains, a glycine- and serine-rich region (called the GS domain) preceding the kinase domain, and a short C-terminal tail. The encoded protein, sometimes termed ALK1, shares similar domain structures with other closely related ALK or activin receptor-like kinase proteins that form a subfamily of receptor serine/threonine kinases. Mutations in this gene are associated with hemorrhagic telangiectasia type 2, also known as Rendu-Osler-Weber syndrome 2. [provided by RefSeq, Jul 2008 ...
Using a mix of wild-type (WT) and caveolin-2 (Cav-2) knockout along with retroviral reexpression approaches, we offer the data for the negative role of Cav-2 in regulating anti-proliferative function and signaling of changing growth matter (TGF-) in endothelial cells (ECs). evidenced by three unbiased proliferation assays: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell count number, and bromodeoxyuridine incorporation and correlated with a lack of TGF-mediated upregulation of cell routine inhibitor Rabbit polyclonal to PAI-3 p27 and following Rebastinib reduced amount of the degrees of hyperphosphorylated (inactive) type of the retinoblastoma protein in Cav-2 reexpressing ECs. Mechanistically, Cav-2 inhibits anti-proliferative action of TGF- by suppressing Alk5-Smad2/3 pathway manifested by reduced magnitude and amount of TGF-induced Smad2/3 phosphorylation aswell as activation of activin receptor-like kinase-5 (Alk5)-Smad2/3 target genes plasminogen activator ...
J:28212 Iseki S, Osumi-Yamashita N, Miyazono K, Franzen P, Ichijo H, Ohtani H, Hayashi Y, Eto K, Localization of transforming growth factor-beta type I and type II receptors in mouse development. Exp Cell Res. 1995 Aug;219(2):339-47 ...
Following myocardial infarction (MI), the heart undergoes a pathological process known as remodeling, which in many instances results in cardiac dysfunction and ultimately heart failure and death. Transforming growth factor-beta (TGF-beta) is a key m
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A fresh water-soluble polysaccharide (longan polysaccharide 1 (LP1)) was extracted and successfully purified from pulp via diethylaminoethyl (DEAE)-cellulose anion-exchange and Sephacryl S-300 HR gel chromatography. HO8910 tumor cells, with inhibition percentages of Tasquinimod supplier 40% and 50%, respectively. In addition, LP1 significantly stimulated the production of the cytokine interferon- (IFN-), increased the activity of murine […]. ...
Mohammad KS, Chen CG, Balooch G, Stebbins E, McKenna CR, Davis H, Niewolna M, Peng XH, Nguyen DH, Ionova-Martin SS, Bracey JW, Hogue WR, Wong DH, Ritchie RO, Suva LJ, Derynck R, Guise TA, Alliston T. Pharmacologic inhibition of the TGF-beta type I receptor kinase has anabolic and anti-catabolic effects on bone. PLoS One. 2009; 4(4):e5275 ...
Purpose: Activin receptor-like kinase 1 (ALK1) is a novel target in angiogenesis. Concurrent targeting of ALK1 and VEGF signaling results in augmented inhibition of tumor growth in renal cell carcinoma (RCC) xenograft models. Dalantercept is an ALK1-receptor fusion protein that acts as a ligand trap for bone morphogenetic proteins 9 and 10. The DART Study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of dalantercept plus axitinib in patients with advanced RCC and determined the optimal dose for further testing.. Experimental Design: Patients received dalantercept 0.6, 0.9, or 1.2 mg/kg subcutaneously every 3 weeks plus axitinib 5 mg by mouth twice daily until disease progression or intolerance.. Results: Twenty-nine patients were enrolled in the dose escalation (n = 15) and expansion (n = 14) cohorts. There were no dose-limiting toxicities or grade 4/5 treatment-related adverse events. In addition to common VEGFR tyrosine kinase inhibitor effects, ...
This multicenter study evaluated the clinical activity and toxicity of ganetespib in molecularly defined cohorts of patients with advanced NSCLCs. Durable objective responses and disease stabilization occurred in the majority of patients with disease harboring ALK gene rearrangement who were crizotinib-naïve. In NSCLCs, ALK rearrangement results in the expression of one of several variants of the EML4-ALK fusion protein, which results in a constitutively active ALK kinase capable of activating downstream signaling cascades that promote cell proliferation and survival (5, 35, 36). In preclinical studies, ALK inhibition has been shown to induce cell death and tumor regression (17, 36, 37). The data from this trial and the recent study of IPI-504 suggest that in addition to direct tyrosine kinase inhibition, ALK can be disabled by Hsp90 inhibition, confirming preclinical predictions (17, 18). The Hsp90-inhibitory activity of ganetespib is further validation for the clinical value of this class of ...
Olsen, Oddrun Elise; Wader, Karin Fahl; Misund, Kristine; Våtsveen, Thea Kristin; Rø, Torstein Baade; Størdal, Berit Fladvad; Moen, Siv Helen; Standal, Therese; Waage, Anders; Sundan, Anders; Holien, Toril. (2013) Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin. TGF-B Superfamily: Signaling in Development and Disease . FASEB; 2013-07-28 - 2013-08-02. ...
8.0 8.1 Bauer, H et al. (2001) The type I serine/threonine kinase receptor Alk8/Lost-a-fin is required for Bmp2b/7 signal transduction during dorsoventral patterning of the zebrafish embryo. Development 128 849-58 PubMed GONUTS page ...
Actriţa de origine portoricană Miriam Colon, cunoscută pentru rolul mamei lui Al Pacino din Scarface (1983), a murit la vârsta de 80 de ani, anunţă Variety.
ALK5 Inhibitor, also known as RepSox, E616452, and SJN2511, is a competitive inhibitor of ALK5. Promotes differentiation of SMCs.
Petrie, K. A., Pointon, J. J., Atukorala, I., Russell, R. G. G., Wordsworth, P. W., & Triffitt, J. T. (2007). Identification of a novel mutation in activin receptor type 1 (ACVR1) in a fibrodysplasia ossificans progressiva (FOP) patient. CALCIFIED TISSUE INTERNATIONAL, 80, S36-S36 ...
Fibrodysplasia ossificans progressiva (FOP; MIM 135100) is a rare autosomal dominant disease characterized by progressive heterotopic ossification of soft connective tissues including skeletal muscle, tendons and ligaments. Individuals with FOP appear normal at birth, except for malformed great toes and thumbs. The ossification begins in early childhood and progresses over the course of a lifetime. It leads to a debilitating ankylosis of all major joints of the axial and appendicular skeleton and most patients will be confined to wheelchair by the third decade of life. Most FOP cases are sporadic, but there are reports of affected siblings. FOP is caused by mutations in the ACVR1 gene that codes for activin A receptor, type I. It belongs to the protein kinase superfamily and functions as a receptor for bone morphogenetic proteins (BMPs). BMPs are extracellular signaling proteins that are critical for the early development of heart, central nervous system, cartilage, and bone. All of the ACVR1 ...
Fibrodysplasia ossificans progressiva (FOP) is a rare and disabling genetic condition characterized by congenital malformations of the great toes and progressive heterotopic ossification (HO) in specific anatomic patterns. {file27251}{file27252}Most cases arise as a result of a spontaneous new mutation.
MONTREAL, CANADA, June 13, 2016 - Clementia is pleased to announce that the Phase 2 Open-label Extension Trial (PVO-1A-202) has been modified to enroll up to 20 new participants and to investigate new palovarotene dosing regimens in participants with fibrodysplasia ossificans progressiva (FOP). The modification to the Phase 2 Open-label extension trial is designated as Part B.. The Phase 2 Trial (Study PVO-1A-201), which is now complete, was designed as an exploratory dose-ranging study that examined the safety and efficacy of two different dosing regimens of palovarotene in participants for acute flare-up. All 40 individuals who completed the Phase 2 trial have enrolled into the Phase 2 Open-label Extension Trial, which provides access to palovarotene to any participant experiencing an eligible flare-up and continues to evaluate the long-term safety and efficacy of palovarotene.. Much has been learned from these studies. Emerging data suggests that the risk to develop heterotopic ossification ...
... (FOP), also known as Stone Man Syndrome, is a very rare inherited disorder in which muscle tissue and connective tis
Looking for online definition of TGF-beta type I receptor in the Medical Dictionary? TGF-beta type I receptor explanation free. What is TGF-beta type I receptor? Meaning of TGF-beta type I receptor medical term. What does TGF-beta type I receptor mean?
We further explored the physiologic significance of the ability of ACVR1[R206H] to respond to activin A in our mouse model of FOP. Inhibition of activin A with a blocking antibody completely inhibited development of HO. Although our results do not exclude the possibility that other ligands may participate, they indicate that activin A (and perhaps the activin A-containing heterodimers, activin AB and AC) must play a major, indeed obligate, role. Moreover, our data were consistent with the idea that activin A, normally produced by cells of the immune system during inflammation (22, 23), is co-opted and reinterpreted by ACVR1[R206H]-expressing cells with osteogenic potential. Hence, activin A may provide the missing link between inflammation and HO in FOP.. We would like to caution, however, that there is a paucity of data implicating activin A as the driver of HO in FOP patients per se; this is largely due to the inability to safely biopsy patients in between, or during, attacks. We cannot ...
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of ...
Results All patients presented small asymptomatic lesions similar to hamartomas at the level of the dorsal medulla and ventral pons, associated with minor brainstem dysmorphisms and abnormal origin of the vestibulocochlear and facial nerves. The size of the brainstem lesions did not correlate with patients age (p=0.061), age at first flare-up (p=0.733), severity of disability (p=0.194), history of head trauma (p=0.415) or hearing loss (p=0.237). The radiologic features and the absence of neurological symptoms were consistent with a benign process. Variable signal abnormalities and/or calcifications of the dentate nuclei were noted in all patients, while basal ganglia abnormalities were present in nine subjects. Brain calcifications positively correlated with patients age (p,0.001) and severity of disability (p=0.002). ...
Myositis ossificans progressiva: …the rare progressive type (myositis ossificans progressiva), group after group of muscles become ossified, until the individual is completely rigid. Breathing and swallowing become difficult, and fatal respiratory infections may occur. Steroid treatment of muscle injury and the use of medications to prevent calcification may slow the progression of…
Fibrous dysplasia is the uncommon bone disorder in which, instead of the normal bone, fibrous (scar-like) tissue develops, thus weakening the bone affected and causing it to be fractured or deformed. Only a single bone is usually affected by fibrous dysplasia, and it is most commonly a long bone in the legs or arms or the skull. This is the forum for discussing anything related to this health condition
Principal Investigator:Kitoh Hiroshi, Project Period (FY):2015-04-01 - 2018-03-31, Research Category:Grant-in-Aid for Challenging Exploratory Research, Research Field:Orthopaedic surgery
Heterotopic ossification is a pathological, non neoplastic process of bone formation at ectopic sites, especially inside mesenchymal soft tissues. The disorder can occur localized or generalized.. Local forms are mostly assigned to the entity of Myositis ossificans circumscripta and involve the skeletal muscles. As a result of trauma, often following total hip replacement, or due to neuropathic disorders, e.g. spinal cord lesions, an intramuscular osteogenesis occurs. The osteogenic stimulation of mesenchymal stem cells seems to be the cause, but the pathobiochemical pathways are not known exactly [1].. The generalized disorder Fibrodysplasia ossificans progressiva (FOP, syn. Myositis ossificans progressiva) is a rare connective tissue desease with autosomal dominant heredity. It is characterized by enchondral ossification of muscle, tendons and ligaments after simple injuries, e.g. intramuscular injection [2-4]. The influence of bone morphogenetic proteins on this disorder seems to be evident ...
The term heterotopic ossification (HO) describes bone formation at an abnormal anatomical site, usually in soft tissue. HO can be classified into the following 3 types: Myositis ossificans progressiva (fibrodysplasia ossificans progressiva) - This disorder is among the rarest genetic conditions, with an incidence of 1 case per 2 million persons.
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of ...
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of ...
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of ...
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of ...
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of ...
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of ...
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of ...
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of ...
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of ...
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of ...
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of ...
Transforming growth factor betas (Tgfbetas) and Bone morphogenetic proteins (Bmps) are pleiotropic cytokines involved in many developmental processes. Organ explant studies have revealed specific roles for Tgfbeta/Bmp ligands in endothelial-mesenchymal transformations (EMT) during the formation of endocardial cushions, precursors of heart valves and septa, and in epicardial-mesenchymal transformations essential for coronary vasculature development. Gene targeting studies in mice demonstrated that the Tgfbetas/Bmps are involved in the ventricular myocardial development and formation of the neural crest-derived aorticopulmonary septum. Tgfbeta/Bmp ligands signal through a repertoire of type I and type II serine/threonine kinase receptors. In our studies, we sought to determine the requirement of Bmp type I receptor Alk2 and Tgfbeta; type I receptor Alk5 for heart development by ablating these receptors specifically in the endocardium (Tie2-Cre), in the myocardium (alphaMHC-Cre and Nkx2.5-Cre), in ...
Transforming growth factor betas (Tgfbetas) and Bone morphogenetic proteins (Bmps) are pleiotropic cytokines involved in many developmental processes. Organ explant studies have revealed specific roles for Tgfbeta/Bmp ligands in endothelial-mesenchymal transformations (EMT) during the formation of endocardial cushions, precursors of heart valves and septa, and in epicardial-mesenchymal transformations essential for coronary vasculature development. Gene targeting studies in mice demonstrated that the Tgfbetas/Bmps are involved in the ventricular myocardial development and formation of the neural crest-derived aorticopulmonary septum. Tgfbeta/Bmp ligands signal through a repertoire of type I and type II serine/threonine kinase receptors. In our studies, we sought to determine the requirement of Bmp type I receptor Alk2 and Tgfbeta; type I receptor Alk5 for heart development by ablating these receptors specifically in the endocardium (Tie2-Cre), in the myocardium (alphaMHC-Cre and Nkx2.5-Cre), in ...
Heterotopic ossification (HO) is a disabling condition associated with neurologic injury, inflammation, and overactive bone morphogenetic protein (BMP) signaling. The inductive factors involved in lesion formation are unknown. We found that the expression of the neuro-inflammatory factor Substance P (SP) is dramatically increased in early lesional tissue in patients who have either fibrodysplasia ossificans progressiva (FOP) or acquired HO, and in three independent mouse models of HO. In Nse-BMP4, a mouse model of HO, robust HO forms in response to tissue injury; however, null mutations of the preprotachykinin (PPT) gene encoding SP prevent HO. Importantly, ablation of SP+ sensory neurons, treatment with an antagonist of SP receptor NK1r, deletion of NK1r gene, or genetic down-regulation of NK1r-expressing mast cells also profoundly inhibit injury-induced HO. These observations establish a potent neuro-inflammatory induction and amplification circuit for BMP-dependent HO lesion formation, and ...
PHILADELPHIA - An international team of scientists, led by researchers at the University of Pennsylvania School of Medicine, is taking the first step in developing a treatment for a rare genetic disorder called fibrodysplasia ossificans progressiva (FOP), in which the bodys skeletal muscles and soft connective tissue turns to bone, immobilizing patients over a lifetime with a second skeleton.. Reporting in the November issue of the Journal of Clinical Investigation senior authors Eileen Shore, PhD, Professor of Genetics and Orthopedics, and Mary Mullins, PhD, Professor of Cell and Developmental Biology, with scientists in Japan and Germany, demonstrated that the mutation that causes FOP mistakenly activates a cascade of biochemical events in soft tissues that kicks off the process of bone development. The linchpin of the cellular signaling gone awry is a receptor for a bone morphogenetic protein, or BMP.. The present study provides the first clear glimpse of how FOP might develop at a cellular ...
In the present experiments, AP has been measured in Alk1+/− and in Alk1+/+ mice by both tail-cuff and radiotelemetry methods. We have used both methods to measure AP because movement restriction necessary for tail-cuff measurement can modify vasoactive responses, especially when the sympathetic nervous system is involved, and because acute (minutes) effects can be difficult to assess by the tail-cuff method. Besides, both acute and prolonged effects of the vasoactive substances have been recorded because the acute and the long-standing consequences of inhibiting or stimulating these regulatory pathways can be different (Emanueli et al., 1997). Measurements of AP by the tail-cuff method and by telemetry showed consistently higher SAP in Alk1+/− than in Alk1+/+ mice, with no significant differences in HR. It should be noted that arterial hypertension has not been reported as a common sign in individuals with hereditary hemorrhagic telangiectasia type 2, a fact that can be explained by the ...
By January 1999, she was given a diagnosis of fibrodysplasia ossificans progressiva (FOP), a rare genetic disease that causes muscle tissue and connective tissue to turn into bone - gradually forming a second skeleton and making it nearly impossible to move.
Cell culture. iPSCs were maintained in primate embryonic stem (ES) cell medium (ReproCELL) supplemented with 4 ng/ml recombinant human FGF2 (Wako Pure Chemical). To activate the production of induced neural crest cells (iNCCs), mTeSR1 medium (STEMCELL Technologies) was used for the feeder-free culturing of iPSCs. The induction and maintenance of iNCCs and iMSCs derived from iPSCs were previously described (43, 45) (Supplemental Figure 1A). Briefly, iNCCs were induced in chemically defined medium (CDM) supplemented with 10 μM SB-431542 and 1 μM CHIR99021 for 7 days. iNCCs were maintained in CDM supplemented with 10 μM SB-431542, 20 ng/ml FGF2, and 20 ng/ml recombinant human EGF (R&D Systems), and we used up to 20 passages in this study. iMSCs were induced and maintained in αMEM (Invitrogen, Thermo Fisher Scientific) supplemented with 10% (v/v) FBS (Nichirei), 5 ng/ml FGF2, and 0.5% penicillin and streptomycin (Invitrogen, Thermo Fisher Scientific). The FOP-iPSCs used in this study (previously ...
Activin receptor type-2B is a protein that in humans is encoded by the ACVR2B gene. ACVR2B is an activin type 2 receptor. ... and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a ... This gene encodes activin A type IIB receptor, which displays a 3- to 4-fold higher affinity for the ligand than activin A type ... resulting in phosphorylation of type I receptors by type II receptors. Type II receptors are considered to be constitutively ...
... is an activin type 2 receptor. This gene encodes activin A type II receptor. Activins are dimeric growth and ... and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a ... resulting in phosphorylation of type I receptors by type II receptors. Type II receptors are considered to be constitutively ... "Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. ...
"Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors". ... It is also known as activin receptor-like kinase 1, or ALK1. This gene encodes a type I cell-surface receptor for the TGF-beta ... "Entrez Gene: ACVRL1 activin A receptor type II-like 1". Olivieri C, Mira E, Delù G, Pagella F, Zambelli A, Malvezzi L, ... "Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2". Nature Genetics. 13 (2 ...
... resulting in phosphorylation of type I receptors by type II receptors. This gene encodes activin A type I receptor which ... and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a ... ACVR1 encodes activin receptor type-1, a BMP type-1 receptor. The mutation causes the ACVR1 protein to have the amino acid ... Activin A receptor, type I (ACVR1) is a protein which in humans is encoded by the ACVR1 gene; also known as ALK-2 (activin ...
ACVR1 encodes activin receptor type-1, a BMP type-1 receptor. The mutation causes substitution of codon 206 from arginine to ... "ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A". stm. ... Feldman, G. "A recurrent mutation in the BMP type I receptor ACVR1 ( HSC'13) causes inherited and sporadic fibrodysplasia ... 2006). "A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans ...
2004). "Activin isoforms signal through type I receptor serine/threonine kinase ALK7". Mol. Cell. Endocrinol. 220 (1-2): 59-65 ... 2001). "The orphan receptor ALK7 and the Activin receptor ALK4 mediate signaling by Nodal proteins during vertebrate ... "SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase ... The activin A receptor also known as ACVR1C or ALK-7 is a protein that in humans is encoded by the ACVR1C gene. ACVR1C is a ...
January 2008). "MicroRNA miR-24 inhibits erythropoiesis by targeting activin type I receptor ALK4". Blood. 111 (2): 588-95. doi ...
"Characterization of type I receptors for transforming growth factor-beta and activin". Science. 264 (5155): 101-4. doi:10.1126/ ... kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Type II receptors bind ligands in ... the absence of type I receptors, but they require their respective type I receptors for signaling, whereas type I receptors ... Bone morphogenetic protein receptor type-1B also known as CDw293 (cluster of differentiation w293) is a protein that in humans ...
A two-week treatment of normal mice with soluble activin type IIB receptor, a molecule that is normally attached to cells and ... Myostatin binds to the activin type II receptor, resulting in a recruitment of either coreceptor Alk-3 or Alk-4. This ... "Regulation of muscle growth by multiple ligands signaling through activin type II receptors". Proceedings of the National ... is thought that binding of myostatin to the soluble activin receptor prevents it from interacting with the cell-bound receptors ...
"Identification and characterization of a PDZ protein that interacts with activin type II receptors". J Biol Chem. 275 (8): 5485 ... 2003). "PKC regulates the delta2 glutamate receptor interaction with S-SCAM/MAGI-2 protein". Biochem. Biophys. Res. Commun. 301 ... 2001). "beta 1-adrenergic receptor association with the synaptic scaffolding protein membrane-associated guanylate kinase ... inverted-2 (MAGI-2). Differential regulation of receptor internalization by MAGI-2 and PSD-95". J. Biol. Chem. 276 (44): 41310- ...
... resulting in phosphorylation of type I receptors by type II receptors. This gene encodes activin A type IB receptor, composed ... and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a ... "Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. ... "Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. ...
"Determination of type I receptor specificity by the type II receptors for TGF-beta or activin". Science. 262 (5135): 900-2. doi ... Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E (March 2000). "Activin receptor ... Choy L, Derynck R (November 1998). "The type II transforming growth factor (TGF)-beta receptor-interacting protein TRIP-1 acts ... It can also decrease the expression levels of cytokine receptors, such as the IL-2 receptor to down-regulate the activity of ...
2005). "The structure of the follistatin:activin complex reveals antagonism of both type I and type II receptor binding". Dev. ... Walsh S, Metter EJ, Ferrucci L, Roth SM (2007). "Activin-type II receptor B (ACVR2B) and follistatin haplotype associations ... 2007). "Activin subunit and receptor expression in normal and cleft human fetal palate tissues". Pediatr. Dev. Pathol. 10 (6): ... In the blood, activin and follistatin are both known to be involved in the inflammatory response following tissue injury or ...
... such as the activin type 2 receptor; and bone morphogenetic protein receptor, type IA. Other LU domain proteins are small ... "Three-finger toxin fold for the extracellular ligand-binding domain of the type II activin receptor serine kinase". Nature ... Ploug, Michael; Ellis, Vincent (1994-08-01). "Structure-function relationships in the receptor for urokinase-type plasminogen ... Other receptors with LU domains include members of the transforming growth factor beta receptor (TGF-beta) superfamily, ...
This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. ... Lebrun JJ, Takabe K, Chen Y, Vale W (January 1999). "Roles of pathway-specific and inhibitory Smads in activin receptor ... This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA ... O'Neill TJ, Zhu Y, Gustafson TA (April 1997). "Interaction of MAD2 with the carboxyl terminus of the insulin receptor but not ...
Crypto is a glycosylphosphatidylinositol-anchored co-receptor that binds nodal and the activin type I ActRIB (ALK)-4 receptor ( ... In the Nodal signaling pathway of embryonic development, Cripto has been shown to have dual function as a co-receptor as well ... Cryptic family protein 1B acts as a receptor for the TGF beta signaling pathway. It has been associated with the translation of ... EGF-CFC proteins' composition as a receptor complex is further solidified by the GPI linkage, making the cell membrane ...
... and BMPR1B and the type II receptor BMPR2. These receptors are also closely related to the activin receptors, ACVR1 and ACVR2. ... kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Type II receptors bind ligands in ... the absence of type I receptors, but they require their respective type I receptors for signaling, whereas type I receptors ... "Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs". Mol. Cell ...
"Regulation of endocytosis of activin type II receptors by a novel PDZ protein through Ral/Ral-binding protein 1-dependent ... involvement of the Ral pathway in receptor endocytosis". J. Cell Sci. 113 (16): 2837-44. PMID 10910768. Awasthi S, Cheng J, ...
"Regulation of endocytosis of activin type II receptors by a novel PDZ protein through Ral/Ral-binding protein 1-dependent ... "Novel factors in regulation of activin signaling". Molecular and Cellular Endocrinology. 225 (1-2): 1-8. doi:10.1016/j.mce. ... "Novel factors in regulation of activin signaling". Molecular and Cellular Endocrinology. 225 (1-2): 1-8. doi:10.1016/j.mce. ... "Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse ...
"Regulation of endocytosis of activin type II receptors by a novel PDZ protein through Ral/Ral-binding protein 1-dependent ... The product of this gene is part of a protein complex that regulates the endocytosis of growth factor receptors. The encoded ... Its expression can negatively affect receptor internalization and inhibit growth factor signaling. Multiple transcript variants ... "Epsin binds to the EH domain of POB1 and regulates receptor-mediated endocytosis". Oncogene. 18 (43): 5915-22. doi:10.1038/sj. ...
... is a recombinant fusion protein derived from human activin receptor type IIb (ActRIIb) linked to a protein derived ...
ACE-011 was a chimeric protein, created by fusing the binding portion of the activin type 2 receptor to part of an antibody; ... a protein therapeutic that was an activin type 2 receptor antagonist intended to treat bone loss. ... the resulting protein binds to activin and prevents it from acting. Knopf took over as CEO in 2007. He became known for showing ...
It is a TGFβ type 1 receptor antagonist. It blocks TGFβ1 and activin associating with the receptor, blocking access to SMAD2. ... By occupying type I receptors for Activin and bone morphogenetic protein (BMP), it also plays a role in negative feedback of ... "Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation". J. Biol ... Lebrun JJ, Takabe K, Chen Y, Vale W (January 1999). "Roles of pathway-specific and inhibitory Smads in activin receptor ...
In the cell surface Dapper2 tightly binds to the active form of the activin type 1 receptors and targets the receptor for ... Activation of the Nodal pathway involves nodal binding to activin and activin-like receptors which leads to phosphorylation of ... The binding of Nodal proteins to activin or activin-like serine/threonine kinase receptors results in the phosphorylation of ... Somehow the reduction of activin receptors would lead to the decrease in activity of different TGFb pathways. Smad proteins are ...
... also known has Activin A receptor, type I (ACVR1), and the other type II receptors BMPRII and ActRIIA. GDF2 and BMP10 are the ... and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery ... an endothelial-specific type I receptor of the TGF-beta receptor family. Endoglin, a type I membrane glycoprotein that forms ... start with a ligand binding with a high affinty type I receptor (ALK1-7) followed by the recruitment of a type II receptor( ...
It may also be used to treat and prevent certain types of thyroid tumors.[1] It is not indicated for weight loss.[1] ... T4 and T3 bind to thyroid receptor proteins in the cell nucleus and cause metabolic effects through the control of DNA ...
Buy our Recombinant Human Activin Receptor Type IIB protein. Ab125577 is a protein fragment produced in Baculovirus infected ... Recombinant Human Activin Receptor Type IIB protein. See all Activin Receptor Type IIB proteins and peptides. ... forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors ... By product type. Proteins and Peptides. Proteomics tools. Agonists, activators, antagonists and inhibitors. Lysates. Multiplex ...
... "Identification of a Novel Mutation in Activin Receptor Type 1 (ACVR1) in a Fibrodysplasia Ossificans Progressiva (FOP) Patient ... "Identification of a Novel Mutation in Activin Receptor Type 1 (ACVR1) in a Fibrodysplasia Ossificans Progressiva (FOP) Patient ... Identification of a novel mutation in activin receptor type 1 (ACVR1) in a fibrodysplasia ossificans progressiva (FOP) patient ...
Identification of human activin and TGFβ type I receptors that form heteromeric kinase complexes with type II receptors. Cell ... A) Activin signals via the type I receptors ACVR1B/1C and Smad2/3 phosphorylation but shares type II receptors (ACVR2A, ACVR2B ... The ability of activins to form nonsignaling complexes with ACVR1 in conjunction with the type II receptors ACVR2A and ACVR2B ... Mutant activin-like kinase 2 in fibrodysplasia ossificans progressiva are activated via T203 by BMP type II receptors. Mol. ...
The seven members of the BMP type-I receptor family, activin receptor-like kinase (ALK) 1-7, play critical roles in human ... type-I receptor family, ALK2. La Jolla recently entered a worldwide, exclusive license agreement with Vanderbilt University ... In turn, the improper activation of these receptor pathways is responsible for a wide range of disease conditions. ... its type previously granted the designation for the same indication. The designation also provides the drug developer with tax ...
Fst from 2mg/Vial Freeze-Dried Polypeptide Powder Follistatin 344 Activin-Binding Protein - Shanghai Shucan Industrial Co., Ltd ... China 2mg/Vial Freeze-Dried Polypeptide Powder Follistatin 344 Activin-Binding Protein, Find details about China Follistatin ... based on activin receptor type IIB (ActRIIB). The molecule inhibits signaling via the ActRIIB receptor binding ... FS is a high-affinity activin-binding protein that can act as an activin antagonist. Two alternatively spliced ...
Characterization of the ligand binding functionality of the extracellular domain of activin receptor type IIb. J Biol Chem. ... This neofunction of Activin-A raised the possibility that the inhibition of Activin-A signaling by Activin-A-specific- ... The type I serine/threonine kinase receptor ActRIA (ALK2) is required for gastrulation of the mouse embryo. Development. 1999; ... BMP type I receptor inhibition reduces heterotopic [corrected] ossification. Nat Med. 2008;14(12):1363-1369.. View this article ...
Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been ... test compared with the DMSO treatment control with Activin-A (. B. -. D. ).Representative data of n. =3. Scale bar: 200 μm (. E ... Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms ... Activin-A enhances mTOR signaling to promote aberrant chondrogenesis in fibrodysplasia ossificans progressiva. ...
ACVR1 encodes activin receptor type-1, a BMP type-1 receptor. The mutation causes substitution of codon 206 from arginine to ... A mutation in the gene ACVR1 (also known as activin-like kinase 2 [ALK-2]) is responsible for the disease. ...
Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been ... Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms ... Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of peripheral myelin protein 22 (PMP22) and is the most ... Activin-A enhances mTOR signaling to promote aberrant chondrogenesis in fibrodysplasia ossificans progressiva. ...
Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been ... Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms ... Selective, inducible deletion of the PTH receptor in Sox9-cre cells demonstrated that PTH receptor expression is required for ... Activin-A enhances mTOR signaling to promote aberrant chondrogenesis in fibrodysplasia ossificans progressiva. ...
Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been ... Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms ... Dinaciclib induced a type I IFN gene signature within the tumor, leading us to hypothesize that dinaciclib potentiates the ... Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of peripheral myelin protein 22 (PMP22) and is the most ...
Arteriovenous malformations in mice lacking activin receptor-like kinase-1. Nat Genet. 2000;26(3):328-331.. View this article ... Clinical manifestations in a large hereditary hemorrhagic telangiectasia (HHT) type 2 kindred. Am J Med Genet. 2000;93(4):320- ... or β3-adrenergic receptors (n = 5). SCR, scrambled siRNA. (L-N) Expression of (L) β1-, (M) β2-, or (N) β3-adrenergic receptors ... or β3-adrenergic receptors (n = 5). Data shown in H-J and L-N were analyzed by Students t test. Data shown in E, F, K, and O ...
A ligand binds to a type 2 receptor, which recruits and trans-phosphorylates a type I receptor. The type I receptor recruits a ... inhibin/activin betaA and betaB and the activin type II and inhibin beta-glycan receptors in the developing human testis". ... There are two activin type two receptors: ACVR2A and ACVR2B. Despite the large amount of processes that these ligands regulate ... The activin type 2 receptors modulate signals for ligands belonging to the transforming growth factor beta superfamily of ...
A ligand binds to a Type two receptor, which recruits and trans-phosphorylate a type I receptor. The type I receptor recruits a ... There are three type I Activin receptors: ACVR1, ACVR1B, and ACVR1C. Each bind to a specific type II receptor-ligand complex. ... The Activin type I receptors transduce signals for a variety of members of the Transforming growth factor beta superfamily of ... This family of cytokines and hormones include activin, Anti-müllerian hormone (AMH), bone morphogenetic proteins (BMPs), and ...
Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Se-Jin Lee, Lori A. Reed, Monique ... Here we describe a potent myostatin inhibitor, a soluble form of the activin type IIB receptor (ACVR2B), which can cause ... Previous studies have demonstrated that myostatin is capable of binding the two activin type II receptors, ACVR2B and, to a ... Finally, we provide genetic evidence that these ligands signal through both activin type II receptors, ACVR2 and ACVR2B, to ...
Rabbit polyclonal Activin Receptor Type IIA antibody. Validated in WB, ICC/IF and tested in Human. Cited in 1 publication(s). ... Anti-Activin Receptor Type IIA antibody. See all Activin Receptor Type IIA primary antibodies. ... forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors ... All lanes : Anti-Activin Receptor Type IIA antibody (ab96793) at 1/10000 dilution. Lane 1 : HeLa whole cell lysate. Lane 2 : ...
Activin receptor type-1. Activin receptor type-1, EC 2.7.11.30 (Activin receptor type I, ACTR-I) (Activin receptor-like kinase ... Activin receptor type-1Imported. ,p>Information which has been imported from another database using automatic procedures.,/p> , ... tr,C9J1R3,C9J1R3_HUMAN Activin receptor type-1 (Fragment) OS=Homo sapiens OX=9606 GN=ACVR1 PE=4 SV=1 ... 2, ALK-2) (Serine/threonine-protein kinase receptor R1, SKR1) (TGF-B superfamily receptor type I, TSR-I) ...
TGF-B superfamily receptor type I. activin A receptor type II-like 1. activin A receptor type IL. activin A receptor, type II- ... ACVRL1 activin A receptor like type 1 [Homo sapiens] ACVRL1 activin A receptor like type 1 [Homo sapiens]. Gene ID:94 ... STKc_ACVR1_ALK1; Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1. ... STKc_ACVR1_ALK1; Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1. ...
type I serine/threonine-protein kinase receptor, Activin/BMP/TGF-beta types ... Blue cells = expressed in wild-type.. Gray triangles = other expression annotations only. (e.g. absence of expression or data ...
Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD ... Receptor for activin A, activin B and inhibin A. Mediates induction of adipogenesis by GDF6. ... forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. ... forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors ...
... type I), Authors: Cláudia A Rainho, Silvia R Rogatto. Published in: Atlas Genet Cytogenet Oncol Haematol. ... sequence identity to activin receptor type II and activin receptor type IIB, transforming growth factor-beta (TGF-beta) type II ... ACVR1(activin A receptor, type I), - ACVR1C (activin A receptor, type IC (ACVR1C),. - CYTIP (cytohesin 1 interacting protein), ... The activin A type I receptor is essential for activin signaling, while type II receptors are required for binding ligands. On ...
Synonyms: ACTR-IIB, ACTRIIB, ActR-IIB, Activin receptor type IIB, Activin receptor type-2B, ... ... Cloning of a second form of activin-betaA cDNA and regulation of activin-betaA subunits and activin type II receptor mRNA ... Expression of type II activin receptor genes during differentiation of human K562 cells and cDNA cloning of the human type IIB ... Production and localization of activins and activin type IIA and IIB receptors by the human endosalpinx. Refaat, B.A., Bahathiq ...
activin A receptor, type IIB , activin receptor type IIB , activin receptor type-2B-like , activin type IIB receptor , activin ... receptor type-2B , ACTR-IIB , testicular activin receptor IIB , ActRIIB type II activin receptor B , Activine receptor 2b ( ... anti-Activin A Receptor, Type IIB (ACVR2B) Antikörper. Bezeichnung:. anti-Activin A Receptor, Type IIB Antikörper (ACVR2B). Auf ... Weitere Produktkategorien zu Activin A Receptor, Type IIB Antikörper * 138 anti-Activin A Receptor, Type IIB Primary Antibodies ...
What is Activin receptor type IIA? Meaning of Activin receptor type IIA medical term. What does Activin receptor type IIA mean? ... Looking for online definition of Activin receptor type IIA in the Medical Dictionary? Activin receptor type IIA explanation ... type-II receptors are required for binding ligands and expression of type-I receptors. After activin binding, type-I receptors ... redirected from Activin receptor type IIA) ACVR2A. A gene on chromosome 2q22.3 that encodes activin receptor type IIA, a ...
Selected quality suppliers for anti-Activin A Receptor Type IB antibodies. ... Order monoclonal and polyclonal Activin A Receptor Type IB antibodies for many applications. ... activin A receptor, type IB , activin A receptor, type 1B , activin type IB receptor , activin receptor type-1B-like , Activin ... receptor type-1B , activin receptor IB , ALK-4 , activin receptor type IB , activin receptor type-1B , activin receptor-like ...
  • Dinaciclib induced a type I IFN gene signature within the tumor, leading us to hypothesize that dinaciclib potentiates the effects of anti-PD1 by eliciting ICD. (jci.org)
  • To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of mesenchymal stromal cells derived from FOP-iPSCs (FOP-iMSCs). (jci.org)
  • The cells were harvested 3 days ( B ), 7 days ( C ), or 6 days ( D and E ) after chondrogenesis induction was performed, with or without Activin-A and inhibitors (10 μM). (jci.org)
  • Furthermore, we show that the effect of the soluble receptor is attenuated but not eliminated in Mstn -/- mice, suggesting that at least one other ligand in addition to myostatin normally functions to limit muscle growth. (pnas.org)
  • The results from the oral presentation titled "ACE-011, A Soluble Activin Receptor Type IIA Fusion Protein, Increases BMD and Improves Microarchitecture in Cynomolgus Monkeys" were presented at The American Society for Bone and Mineral Research (ASBMR) 29th Annual Meeting held in Honolulu, Hawaii, USA, September 16 - 19, 2007. (thefreedictionary.com)
  • In this study we investigated the action of RAP-031, a soluble activin receptor type IIB (ActRIIB) comprised of a form of the ActRIIB extracellular domain linked to a murine Fc, and the NF-κB inhibitor, ursodeoxycholic acid (UDCA), on the whole body strength of mdx mice. (nih.gov)
  • However, certain effects of activin, like induction of follicle stimulating hormone secretion in rat pituitary cells were not observed for OP-1. (rupress.org)
  • Activin-A up-regulates type I activin receptor mRNA levels in human immortalized extravillous trophoblast cells. (nih.gov)
  • To further examine the role and signaling mechanism of activin in regulating placental function, the steady-state level of activin type I receptor (ActRI) mRNA in immortalized extravillous trophoblasts (IEVT) cells was measured using competitive PCR (cPCR). (nih.gov)
  • ActRI mRNA levels were increased in a dose-dependent manner by activin-A with the maximal effect observed at the dose of 10 ng/ml. (nih.gov)
  • Time course studies revealed that activin-A had maximal effects on ActRI mRNA levels at 6 hours after treatment. (nih.gov)
  • These findings provide evidence, for the first time, that activin-A modulates ActRI mRNA levels in human trophoblast cells. (nih.gov)
  • Molecular docking simulation based in-silico virtual screening technique is used in current experimental study for developing potent inhibitor molecules for activin receptor type IIB of humans for treatment of anaemia. (alliedacademies.org)
  • In brief, treatment with a novel TGF-beta type I receptor inhibitor, GW788388, significantly reduced TGF-beta activity, leading to the attenuation of systolic dysfunction and left ventricular remodeling in an experimental rat model of MI. (biomedsearch.com)
  • The binding affinity of OP-1 to ActR-II was two- to threefold lower than that of activin A. A transcriptional activation signal was transduced after binding of OP-1 to the complex of ActR-I and ActR-II, or that of BMPR-IB and ActR-II. (rupress.org)
  • The morphological defect is not observed in mutants for the TGFβ receptor baboon , and epistasis tests showed that baboon is epistatic to Smad2 for disc overgrowth. (biologists.org)