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.
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.
A family of CELL SURFACE RECEPTORS that bind BONE MORPHOGENETIC PROTEINS. They are PROTEIN-SERINE-THREONINE KINASES that mediate SIGNAL TRANSDUCTION PATHWAYS through SMAD 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.
A potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into OSTEOBLASTS.
A receptor-regulated smad protein that undergoes PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS. It regulates BONE MORPHOGENETIC PROTEIN signaling and plays an essential role in EMBRYONIC DEVELOPMENT.
A bone morphogenetic protein that is a potent inducer of bone formation. It also functions as a regulator of MESODERM formation during EMBRYONIC DEVELOPMENT.
Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.
Cell surface receptors that bind growth or trophic factors with high affinity, triggering intracellular responses which influence the growth, differentiation, or survival of cells.
A family of smad proteins that undergo PHOSPHORYLATION by CELL SURFACE RECEPTORS in response to TRANSFORMING GROWTH FACTOR BETA; ACTIVIN; or BONE MORPHOGENETIC PROTEIN signaling.
A bone morphogenetic protein that is widely expressed during EMBRYONIC DEVELOPMENT. It is both a potent osteogenic factor and a specific regulator of nephrogenesis.
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.
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.
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).
A bone morphogenetic protein that is a potent inducer of BONE formation. It plays additional roles in regulating CELL DIFFERENTIATION of non-osteoblastic cell types and epithelial-mesenchymal interactions.
The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs.
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.
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.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A pyrrolizidine alkaloid and a toxic plant constituent that poisons livestock and humans through the ingestion of contaminated grains and other foods. The alkaloid causes pulmonary artery hypertension, right ventricular hypertrophy, and pathological changes in the pulmonary vasculature. Significant attenuation of the cardiopulmonary changes are noted after oral magnesium treatment.
A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principle cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.
A bone morphogenetic protein that may play a role in CARTILAGE formation. It is a potent regulator of the growth of CHONDROCYTES and the synthesis of cartilage matrix proteins. Evidence for its role in cartilage formation can be seen in MICE, where genetic mutations that cause loss of bone morphogenetic protein 5 function result in the formation of small malformed ears.
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.
A bone morphogenetic protein that is found at high concentrations in a purified osteoinductive protein fraction from BONE. Bone morphogenetic protein 3 is referred to as osteogenin, however it may play a role in variety of developmental processes.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A receptor-regulated smad protein that undergoes PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS. It regulates BONE MORPHOGENETIC PROTEIN signaling and is essential for PHYSIOLOGICAL ANGIOGENESIS.
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.
A protein that plays a role in GRANULOSA CELLS where it regulates folliculogenesis. Mutations in the gene for bone morphogenetic protein 15 are linked to reproductive abnormalities such as PREMATURE OVARIAN FAILURE.
A superfamily of small proteins which are involved in the MEMBRANE FUSION events, intracellular protein trafficking and secretory processes. They share a homologous SNARE motif. The SNARE proteins are divided into subfamilies: QA-SNARES; QB-SNARES; QC-SNARES; and R-SNARES. The formation of a SNARE complex (composed of one each of the four different types SNARE domains (Qa, Qb, Qc, and R)) mediates MEMBRANE FUSION. Following membrane fusion SNARE complexes are dissociated by the NSFs (N-ETHYLMALEIMIDE-SENSITIVE FACTORS), in conjunction with SOLUBLE NSF ATTACHMENT PROTEIN, i.e., SNAPs (no relation to SNAP 25.)
A bone morphogenetic protein family member that includes an active tolloid-like metalloproteinase domain. The metalloproteinase activity of bone morphogenetic protein 1 is specific for the removal of the C-propeptide of PROCOLLAGEN and may act as a regulator of EXTRACELLULAR MATRIX deposition. Alternative splicing of MRNA for bone morphogenetic protein 1 results in the production of several PROTEIN ISOFORMS.
The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.
The continuous turnover of BONE MATRIX and mineral that involves first an increase in BONE RESORPTION (osteoclastic activity) and later, reactive BONE FORMATION (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium HOMEOSTASIS. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as OSTEOPOROSIS.
An inhibitory Smad protein that negatively regulates the SIGNAL TRANSDUCTION PATHWAYS from BONE MORPHOGENETIC PROTEIN RECEPTORS. Smad6 inhibits PHOSPHORYLATION of SMAD2 PROTEIN and SMAD3 PROTEIN.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
A receptor-regulated smad protein that undergoes PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS and regulates BONE MORPHOGENETIC PROTEIN signaling.
The process of bone formation. Histogenesis of bone including ossification.
A subfamily of Q-SNARE PROTEINS which occupy the same position as syntaxin 1A in the SNARE complex and which also are most similar to syntaxin 1A in their AMINO ACID SEQUENCE. This subfamily is also known as the syntaxins, although a few so called syntaxins are Qc-SNARES.
A growth differentiation factor that plays a regulatory role as a paracrine factor for a diverse array of cell types during EMBRYONIC DEVELOPMENT and in the adult tissues. Growth differentiation factor 2 is also a potent regulator of CHONDROGENESIS and was previously referred to as bone morphogenetic protein 9.
Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.
Renewal or repair of lost bone tissue. It excludes BONY CALLUS formed after BONE FRACTURES but not yet replaced by hard bone.
The amount of mineral per square centimeter of BONE. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by X-RAY ABSORPTIOMETRY or TOMOGRAPHY, X RAY COMPUTED. Bone density is an important predictor for OSTEOPOROSIS.
A family of BONE MORPHOGENETIC PROTEIN-related proteins that are primarily involved in regulation of CELL DIFFERENTIATION.
SNARE proteins where the central amino acid residue of the SNARE motif is an ARGININE. They are classified separately from the Q-SNARE PROTEINS where the central amino acid residue of the SNARE motif is a GLUTAMINE. This subfamily contains the vesicle associated membrane proteins (VAMPs) based on similarity to the prototype for the R-SNAREs, VAMP2 (synaptobrevin 2).
A growth differentiation factor that plays a role in early CHONDROGENESIS and joint formation.
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.
The growth and development of bones from fetus to adult. It includes two principal mechanisms of bone growth: growth in length of long bones at the epiphyseal cartilages and growth in thickness by depositing new bone (OSTEOGENESIS) with the actions of OSTEOBLASTS and OSTEOCLASTS.
A broad category of proteins involved in the formation, transport and dissolution of TRANSPORT VESICLES. They play a role in the intracellular transport of molecules contained within membrane vesicles. Vesicular transport proteins are distinguished from MEMBRANE TRANSPORT PROTEINS, which move molecules across membranes, by the mode in which the molecules are transported.
A bone morphogenetic protein that plays an essential role in the regulation of ovarian folliculogenesis.
Extracellular substance of bone tissue consisting of COLLAGEN fibers, ground substance, and inorganic crystalline minerals and salts.
A synaptic membrane protein involved in MEMBRANE FUSION of SYNAPTIC VESICLES with the presynaptic membranes. It is the prototype member of the R-SNARE PROTEINS.
Bone loss due to osteoclastic activity.
Transport proteins that carry specific substances in the blood or across cell membranes.
A ubiquitous target SNARE protein that interacts with SYNTAXIN and SYNAPTOBREVIN. It is a core component of the machinery for intracellular MEMBRANE FUSION. The sequence contains 2 SNARE domains, one is the prototype for the Qb-SNARES, and the other is the prototype for the Qc-SNARES.
A growth differentiation factor that plays a role in the neural differentiation, specifically in the retinal development of the EYE.
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.
A neuronal cell membrane protein that combines with SNAP-25 and SYNAPTOBREVIN 2 to form a SNARE complex that leads to EXOCYTOSIS.
A subfamily of Q-SNARE PROTEINS which occupy the same position in the SNARE complex as the N-terminal SNARE domain of SNAP-25 and which also are most similar to the N-terminal region of SNAP-25 in their AMINO ACID SEQUENCE.
Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.
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.
Tumors or cancer located in bone tissue or specific BONES.
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
Diseases of BONES.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
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.
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.
The processes occurring in early development that direct morphogenesis. They specify the body plan ensuring that cells will proceed to differentiate, grow, and diversify in size and shape at the correct relative positions. Included are axial patterning, segmentation, compartment specification, limb position, organ boundary patterning, blood vessel patterning, etc.
The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A family of proteins involved in intracellular membrane trafficking. They interact with SYNTAXINS and play important roles in vesicular docking and fusion during EXOCYTOSIS. Their name derives from the fact that they are related to Unc-18 protein, C elegans.
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.
A negative regulator of BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS that blocks activation of CYCLIN-DEPENDENT KINASE INHIBITOR P16 and is de-regulated in a variety of NEOPLASMS.
A subfamily of Q-SNARE PROTEINS which occupy the same position in the SNARE complex as the C-terminal SNARE domain of SNAP-25 and which also are most similar to the C-terminal region of SNAP-25 in their AMINO ACID SEQUENCE.

Convergence of transforming growth factor-beta and vitamin D signaling pathways on SMAD transcriptional coactivators. (1/237)

Cell proliferation and differentiation are regulated by growth regulatory factors such as transforming growth factor-beta (TGF-beta) and the liphophilic hormone vitamin D. TGF-beta causes activation of SMAD proteins acting as coactivators or transcription factors in the nucleus. Vitamin D controls transcription of target genes through the vitamin D receptor (VDR). Smad3, one of the SMAD proteins downstream in the TGF-beta signaling pathway, was found in mammalian cells to act as a coactivator specific for ligand-induced transactivation of VDR by forming a complex with a member of the steroid receptor coactivator-1 protein family in the nucleus. Thus, Smad3 may mediate cross-talk between vitamin D and TGF-beta signaling pathways.  (+info)

A Meis family protein caudalizes neural cell fates in Xenopus. (2/237)

A homologue of the Drosophila homothorax (hth) gene, Xenopus Meis3 (XMeis3), was cloned from Xenopus laevis. XMeis3 is expressed in a single stripe of cells in the early neural plate stage. By late neurula, the gene is expressed predominantly in rhombomeres two, three and four, and in the anterior spinal cord. Ectopic expression of RNA encoding XMeis3 protein causes anterior neural truncations with a concomitant expansion of hindbrain and spinal cord. Ectopic XMeis3 expression inhibits anterior neural induction in neuralized animal cap ectoderm explants without perturbing induction of pan-neural markers. In naive animal cap ectoderm, ectopic XMeis3 expression activates transcription of the posteriorly expressed neural markers, but not pan-neural markers. These results suggest that caudalizing proteins, such as XMeis3, can alter A-P patterning in the nervous system in the absence of neural induction. Regionally expressed proteins like XMeis3 could be required to overcome anterior signals and to specify posterior cell fates along the A-P axis.  (+info)

Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300. (3/237)

The cytokines LIF (leukemia inhibitory factor) and BMP2 (bone morphogenetic protein-2) signal through different receptors and transcription factors, namely STATs (signal transducers and activators of transcription) and Smads. LIF and BMP2 were found to act in synergy on primary fetal neural progenitor cells to induce astrocytes. The transcriptional coactivator p300 interacts physically with STAT3 at its amino terminus in a cytokine stimulation-independent manner, and with Smad1 at its carboxyl terminus in a cytokine stimulation-dependent manner. The formation of a complex between STAT3 and Smad1, bridged by p300, is involved in the cooperative signaling of LIF and BMP2 and the subsequent induction of astrocytes from neural progenitors.  (+info)

A functional bone morphogenetic protein system in the ovary. (4/237)

Bone morphogenetic proteins (BMPs) comprise a large group of polypeptides in the transforming growth factor beta superfamily with essential physiological functions in morphogenesis and organogenesis in both vertebrates and invertebrates. At present, the role of BMPs in the reproductive system of any species is poorly understood. Here, we have established the existence of a functional BMP system in the ovary, replete with ligand, receptor, and novel cellular functions. In situ hybridization histochemistry identified strong mRNA labeling for BMP-4 and -7 in the theca cells and BMP receptor types IA, IB, and II in the granulosa cells and oocytes of most follicles in ovaries of normal cycling rats. To explore the paracrine function of this BMP system, we examined the effects of recombinant BMP-4 and -7 on FSH (follicle-stimulating hormone)-induced rat granulosa cytodifferentiation in serum-free medium. Both BMP-4 and -7 regulated FSH action in positive and negative ways. Specifically, physiological concentrations of the BMPs enhanced and attenuated the stimulatory action of FSH on estradiol and progesterone production, respectively. These effects were dose- and time-dependent. Furthermore, the BMPs increased granulosa cell sensitivity to FSH. Thus, BMPs have now been identified as molecules that differentially regulate FSH-dependent estradiol and progesterone production in a way that reflects steroidogenesis during the normal estrous cycle. As such, it can be hypothesized that BMPs might be the long-sought "luteinization inhibitor" in Graafian follicles during their growth and development.  (+info)

Characterization of osteoblastic differentiation of stromal cell line ST2 that is induced by ascorbic acid. (5/237)

The stromal cell line ST2, derived from mouse bone marrow, differentiated into osteoblast-like cells in response to ascorbic acid. Ascorbic acid induced alkaline phosphatase (ALPase) activity, the expression of mRNAs for proteins that are markers of osteoblastic differentiation, the deposition of calcium, and the formation of mineralized nodules by ST2 cells. We investigated the mechanism whereby ascorbic acid induced the differentiation of ST2 cells. Inhibitors of the formation of collagen triple helices completely blocked the effects of ascorbic acid on ST2 cells, an indication that matrix formation by type I collagen is essential for the induction of osteoblastic differentiation of ST2 cells by ascorbic acid. We furthermore examined the effects of bone morphogenetic proteins (BMPs) on the differentiation of ST2 cells induced by ascorbic acid. Ascorbic acid had no effect on the expression of mRNAs for BMP-4 and the BMP receptors. However, a soluble form of BMP receptor IA inhibited the induction of ALPase activity by ascorbic acid. These results suggest that ascorbic acid might promote the differentiation of ST2 cells into osteoblast-like cells by inducing the formation of a matrix of type I collagen, with subsequent activation of the signaling pathways that involve BMPs.  (+info)

A role for the homeobox gene Xvex-1 as part of the BMP-4 ventral signaling pathway. (6/237)

BMP-4 is believed to play a central role in the patterning of the mesoderm by providing a strong ventral signal. As part of this ventral patterning signal, BMP-4 has to activate a number of transcription factors to fulfill this role. Among the transcription factors regulated by BMP-4 are the Xvent and the GATA genes. A novel homeobox gene has been isolated termed Xvex-1 which represents a new class of homeobox genes. Transcription of Xvex-1 initiates soon after the midblastula transition. Xvex-1 transcripts undergo spatial restriction from the onset of gastrulation to the ventral marginal zone, and the transcripts will remain in this localization including at the tailbud stage in the proctodeum. Expression of Xvex-1 during gastrula stages requires normal BMP-4 activity as evidenced from the injection of BMP-4, Smad1, Smad5 and Smad6 mRNA and antisense BMP-4 RNA. Xvex-1 overexpression ventralizes the Xenopus embryo in a dose dependent manner. Partial loss of Xvex-1 activity induced by antisense RNA injection results in the dorsalization of embryos and the induction of secondary axis formation. Xvex-1 can rescue the effects of overexpressing the dominant negative BMP receptor. These results place Xvex-1 downstream of BMP-4 during gastrulation and suggest that it represents a novel homeobox family in Xenopus which is part of the ventral signaling pathway.  (+info)

Self-organization of periodic patterns by dissociated feather mesenchymal cells and the regulation of size, number and spacing of primordia. (7/237)

Periodic patterning is a fundamental organizing process in biology. Using a feather reconstitution assay, we traced back to the initial stage of the patterning process. Cells started from an equivalent state and self-organized into a periodic pattern without previous cues or sequential propagation. When different numbers of dissociated mesenchymal cells were confronted with a piece of same-sized epithelium, the size of feather primordia remained constant, not the number or interbud spacing, suggesting size determination is intrinsic to dissociated cells. Increasing bone morphogenetic protein (BMP) receptor expression in mesenchymal cells decreased the size of primordia while antagonizing the BMP pathway with Noggin increased the size of primordia. A threshold number of mesenchymal cells with a basal level of adhesion molecules such as NCAM were sufficient to trigger the patterning process. The process is best visualized by the progressive restriction of beta-catenin transcripts in the epidermis. Therefore, feather size, number and spacing are modulated through the available morphogen ligands and receptors in the system.  (+info)

Involvement of the small GTPases XRhoA and XRnd1 in cell adhesion and head formation in early Xenopus development. (8/237)

The Rho family of small GTPases regulates a variety of cellular functions, including the dynamics of the actin cytoskeleton, cell adhesion, transcription, cell growth and membrane trafficking. We have isolated the first Xenopus homologs of the Rho-like GTPases RhoA and Rnd1 and examined their potential roles in early Xenopus development. We found that Xenopus Rnd1 (XRnd1) is expressed in tissues undergoing extensive morphogenetic changes, such as marginal zone cells involuting through the blastopore, somitogenic mesoderm during somite formation and neural crest cells. XRnd1 also causes a severe loss of cell adhesion in overexpression experiments. These data and the expression pattern suggest that XRnd1 regulates morphogenetic movements by modulating cell adhesion in early embryos. Xenopus RhoA (XRhoA) is a potential XRnd1 antagonist, since overexpression of XRhoA increases cell adhesion in the embryo and reverses the disruption of cell adhesion caused by XRnd1. In addition to the potential roles of XRnd1 and XRhoA in the regulation of cell adhesion, we find a role for XRhoA in axis formation. When coinjected with dominant-negative BMP receptor (tBR) in the ventral side of the embryo, XRhoA causes the formation of head structures resembling the phenotype seen after coinjection of wnt inhibitors with dominant-negative BMP receptor. Since dominant-negative XRhoA is able to reduce the formation of head structures, we propose that XRhoA activity is essential for head formation. Thus, XRhoA may have a dual role in the embryo by regulating cell adhesion properties and pattern formation.  (+info)

Bone morphogenetic protein receptors, type II (BMPR2) are a type of cell surface receptor that bind to bone morphogenetic proteins (BMPs), which are growth factors involved in the regulation of various cellular processes such as cell proliferation, differentiation, and apoptosis. BMPR2 is a serine/threonine kinase receptor and forms a complex with type I BMP receptors upon BMP binding. This complex activation leads to the phosphorylation and activation of downstream signaling molecules, including SMAD proteins, which ultimately regulate gene transcription.

Mutations in the BMPR2 gene have been associated with several genetic disorders, most notably pulmonary arterial hypertension (PAH), a rare but life-threatening condition characterized by increased pressure in the pulmonary arteries that supply blood to the lungs. In addition, BMPR2 mutations have also been linked to Marfan syndrome, a genetic disorder that affects connective tissue and can cause skeletal, cardiovascular, and ocular abnormalities.

Bone morphogenetic protein receptors (BMPRs) are a group of transmembrane serine/threonine kinase receptors that play a crucial role in the signaling pathway of bone morphogenetic proteins (BMPs), which are growth factors involved in various biological processes including cell proliferation, differentiation, and apoptosis.

Type I BMPRs include three subtypes: activin receptor-like kinase 2 (ALK2), ALK3 (also known as BMPR-IA), and ALK6 (also known as BMPR-IB). These receptors form a complex with type II BMPRs upon binding of BMP ligands to their extracellular domains. The activation of the receptor complex leads to the phosphorylation of intracellular signaling molecules, such as SMAD proteins, which then translocate to the nucleus and regulate gene expression.

Mutations in type I BMPRs have been associated with several genetic disorders, including hereditary hemorrhagic telangiectasia (HHT), a vascular dysplasia disorder characterized by the formation of abnormal blood vessels. Additionally, alterations in BMP signaling pathways have been implicated in various human diseases, such as cancer, fibrosis, and bone disorders.

Bone morphogenetic protein (BMP) receptors are a type of cell surface receptor that play a crucial role in bone and cartilage development, as well as in other biological processes such as wound healing and embryonic development. These receptors are part of the TGF-β (transforming growth factor-beta) superfamily and are composed of two types of subunits: type I and type II.

Type I BMP receptors include BMPR1A, BMPR1B, and ACTRIIA/B. Type II BMP receptors include BMPR2, ACVR2A, and ACVR2B. When BMPs bind to these receptors, they initiate a signaling cascade that leads to the activation of downstream targets involved in bone formation, cartilage development, and other processes.

Mutations in BMP receptor genes have been associated with various genetic disorders, including fibrodysplasia ossificans progressiva (FOP), a rare condition characterized by the abnormal formation of bone in muscles, tendons, and ligaments. Additionally, dysregulation of BMP signaling has been implicated in diseases such as cancer, where it can contribute to tumor growth and metastasis.

Bone Morphogenetic Proteins (BMPs) are a group of growth factors that play crucial roles in the development, growth, and repair of bones and other tissues. They belong to the Transforming Growth Factor-β (TGF-β) superfamily and were first discovered when researchers found that certain proteins extracted from demineralized bone matrix had the ability to induce new bone formation.

BMPs stimulate the differentiation of mesenchymal stem cells into osteoblasts, which are the cells responsible for bone formation. They also promote the recruitment and proliferation of these cells, enhancing the overall process of bone regeneration. In addition to their role in bone biology, BMPs have been implicated in various other biological processes, including embryonic development, wound healing, and the regulation of fat metabolism.

There are several types of BMPs (BMP-2, BMP-4, BMP-7, etc.) that exhibit distinct functions and expression patterns. Due to their ability to stimulate bone formation, recombinant human BMPs have been used in clinical applications, such as spinal fusion surgery and non-healing fracture treatment. However, the use of BMPs in medicine has been associated with certain risks and complications, including uncontrolled bone growth, inflammation, and cancer development, which necessitates further research to optimize their therapeutic potential.

Bone Morphogenetic Protein 2 (BMP-2) is a growth factor that belongs to the transforming growth factor-beta (TGF-β) superfamily. It plays a crucial role in bone and cartilage formation, as well as in the regulation of wound healing and embryonic development. BMP-2 stimulates the differentiation of mesenchymal stem cells into osteoblasts, which are cells responsible for bone formation.

BMP-2 has been approved by the US Food and Drug Administration (FDA) as a medical device to promote bone growth in certain spinal fusion surgeries and in the treatment of open fractures that have not healed properly. It is usually administered in the form of a collagen sponge soaked with recombinant human BMP-2 protein, which is a laboratory-produced version of the natural protein.

While BMP-2 has shown promising results in some clinical applications, its use is not without risks and controversies. Some studies have reported adverse effects such as inflammation, ectopic bone formation, and increased rates of cancer, which have raised concerns about its safety and efficacy. Therefore, it is essential to weigh the benefits and risks of BMP-2 therapy on a case-by-case basis and under the guidance of a qualified healthcare professional.

Smad1 is a protein that belongs to the Smad family, which are intracellular signaling proteins that play a critical role in the transforming growth factor-beta (TGF-β) signaling pathway. Smad1 is primarily involved in the bone morphogenetic protein (BMP) branch of the TGF-β superfamily.

When BMPs bind to their receptors on the cell surface, they initiate a signaling cascade that leads to the phosphorylation and activation of Smad1. Once activated, Smad1 forms a complex with other Smad proteins, known as a Smad complex, which then translocates into the nucleus. In the nucleus, the Smad complex interacts with various DNA-binding proteins and transcription factors to regulate gene expression.

Smad1 plays crucial roles in several biological processes, including embryonic development, cell differentiation, and tissue homeostasis. Dysregulation of Smad1 signaling has been implicated in a variety of human diseases, such as cancer, fibrosis, and skeletal disorders.

Bone Morphogenetic Protein 4 (BMP-4) is a growth factor that belongs to the transforming growth factor-beta (TGF-β) superfamily. It plays crucial roles in various biological processes, including embryonic development, cell growth, and differentiation. In the skeletal system, BMP-4 stimulates the formation of bone and cartilage by inducing the differentiation of mesenchymal stem cells into chondrocytes and osteoblasts. It also regulates the maintenance and repair of bones throughout life. An imbalance in BMP-4 signaling has been associated with several skeletal disorders, such as heterotopic ossification and osteoarthritis.

Pulmonary hypertension is a medical condition characterized by increased blood pressure in the pulmonary arteries, which are the blood vessels that carry blood from the right side of the heart to the lungs. This results in higher than normal pressures in the pulmonary circulation and can lead to various symptoms and complications.

Pulmonary hypertension is typically defined as a mean pulmonary artery pressure (mPAP) greater than or equal to 25 mmHg at rest, as measured by right heart catheterization. The World Health Organization (WHO) classifies pulmonary hypertension into five groups based on the underlying cause:

1. Pulmonary arterial hypertension (PAH): This group includes idiopathic PAH, heritable PAH, drug-induced PAH, and associated PAH due to conditions such as connective tissue diseases, HIV infection, portal hypertension, congenital heart disease, and schistosomiasis.
2. Pulmonary hypertension due to left heart disease: This group includes conditions that cause elevated left atrial pressure, such as left ventricular systolic or diastolic dysfunction, valvular heart disease, and congenital cardiovascular shunts.
3. Pulmonary hypertension due to lung diseases and/or hypoxia: This group includes chronic obstructive pulmonary disease (COPD), interstitial lung disease, sleep-disordered breathing, alveolar hypoventilation disorders, and high altitude exposure.
4. Chronic thromboembolic pulmonary hypertension (CTEPH): This group includes persistent obstruction of the pulmonary arteries due to organized thrombi or emboli.
5. Pulmonary hypertension with unclear and/or multifactorial mechanisms: This group includes hematologic disorders, systemic disorders, metabolic disorders, and other conditions that can cause pulmonary hypertension but do not fit into the previous groups.

Symptoms of pulmonary hypertension may include shortness of breath, fatigue, chest pain, lightheadedness, and syncope (fainting). Diagnosis typically involves a combination of medical history, physical examination, imaging studies, and invasive testing such as right heart catheterization. Treatment depends on the underlying cause but may include medications, oxygen therapy, pulmonary rehabilitation, and, in some cases, surgical intervention.

Growth factor receptors are a type of cell surface receptor that bind to specific growth factors, which are signaling molecules that play crucial roles in regulating various cellular processes such as growth, differentiation, and survival. These receptors have an extracellular domain that can recognize and bind to the growth factor and an intracellular domain that can transduce the signal into the cell through a series of biochemical reactions.

There are several types of growth factors, including fibroblast growth factors (FGFs), epidermal growth factors (EGFs), vascular endothelial growth factors (VEGFs), and transforming growth factors (TGFs). Each type of growth factor has its own specific receptor or family of receptors.

Once a growth factor binds to its receptor, it triggers a cascade of intracellular signaling events that ultimately lead to changes in gene expression, protein synthesis, and other cellular responses. These responses can include the activation of enzymes, the regulation of ion channels, and the modulation of cytoskeletal dynamics.

Abnormalities in growth factor receptor signaling have been implicated in various diseases, including cancer, developmental disorders, and autoimmune diseases. For example, mutations in growth factor receptors can lead to uncontrolled cell growth and division, which is a hallmark of cancer. Therefore, understanding the structure and function of growth factor receptors has important implications for the development of new therapies for these diseases.

Receptor-regulated Smad proteins (R-Smads) are a subgroup of the Smad family of intracellular signaling proteins that play a critical role in mediating signals from the transforming growth factor-β (TGF-β) superfamily of cytokines and hormones. In humans, there are three types of R-Smads: Smad1, Smad2, Smad3, Smad5, and Smad8/9.

R-Smads are directly phosphorylated by the type I TGF-β receptor kinases upon ligand binding, which leads to their activation and subsequent translocation into the nucleus. Once in the nucleus, R-Smads form complexes with other transcription factors and co-regulators to regulate the expression of target genes involved in various cellular processes such as proliferation, differentiation, apoptosis, migration, and extracellular matrix production.

R-Smad signaling is tightly regulated by several mechanisms, including inhibitory Smads (I-Smads), ubiquitination, and phosphatases, to ensure proper signal transduction and prevent aberrant activation of the pathway. Dysregulation of R-Smad signaling has been implicated in various human diseases, including fibrosis, cancer, and developmental disorders.

Bone Morphogenetic Protein 7 (BMP-7) is a growth factor belonging to the transforming growth factor-beta (TGF-β) superfamily. It plays crucial roles in the development and maintenance of various tissues, including bones, cartilages, and kidneys. In bones, BMP-7 stimulates the differentiation of mesenchymal stem cells into osteoblasts, which are bone-forming cells, thereby promoting bone formation and regeneration. It also has potential therapeutic applications in the treatment of various musculoskeletal disorders, such as fracture healing, spinal fusion, and osteoporosis.

Smad proteins are a family of intracellular signaling molecules that play a crucial role in the transmission of signals from the cell surface to the nucleus in response to transforming growth factor β (TGF-β) superfamily ligands. These ligands include TGF-βs, bone morphogenetic proteins (BMPs), activins, and inhibins.

There are eight mammalian Smad proteins, which are categorized into three classes based on their function: receptor-regulated Smads (R-Smads), common mediator Smads (Co-Smads), and inhibitory Smads (I-Smads). R-Smads include Smad1, Smad2, Smad3, Smad5, and Smad8/9, while Smad4 is the only Co-Smad. The I-Smads consist of Smad6 and Smad7.

Upon TGF-β superfamily ligand binding to their transmembrane serine/threonine kinase receptors, R-Smads are phosphorylated and form complexes with Co-Smad4. These complexes then translocate into the nucleus, where they regulate the transcription of target genes involved in various cellular processes, such as proliferation, differentiation, apoptosis, migration, and extracellular matrix production. I-Smads act as negative regulators of TGF-β signaling by competing with R-Smads for receptor binding or promoting the degradation of receptors and R-Smads.

Dysregulation of Smad protein function has been implicated in various human diseases, including fibrosis, cancer, and developmental disorders.

Activin receptors, type II, are a subgroup of serine/threonine kinase receptors that play a crucial role in signal transduction pathways involved in various biological processes, including cell growth, differentiation, and apoptosis. There are two types of activin receptors, Type IIA (ACVR2A) and Type IIB (ACVR2B), which are single-pass transmembrane proteins with an extracellular domain that binds to activins and a cytoplasmic domain with kinase activity.

Activins are dimeric proteins that belong to the transforming growth factor-β (TGF-β) superfamily, and they play essential roles in regulating developmental processes, reproduction, and homeostasis. Activin receptors, type II, function as primary binding sites for activins, forming a complex with Type I activin receptors (ALK4, ALK5, or ALK7) to initiate downstream signaling cascades.

Once the activin-receptor complex is formed, the intracellular kinase domain of the Type II receptor phosphorylates and activates the Type I receptor, which in turn propagates the signal by recruiting and phosphorylating downstream effectors such as SMAD proteins. Activated SMADs then form a complex and translocate to the nucleus, where they regulate gene expression.

Dysregulation of activin receptors, type II, has been implicated in various pathological conditions, including cancer, fibrosis, and developmental disorders. Therefore, understanding their function and regulation is essential for developing novel therapeutic strategies to target these diseases.

Activin receptors, type I are serine/threonine kinase receptors that play a crucial role in the activin signaling pathway. There are two types of activin receptors, Type I (ALK2, ALK4, and ALK7) and Type II (ActRII and ActRIIB). Activin receptors, type I are transmembrane proteins that bind to activins, which are cytokines belonging to the TGF-β superfamily.

Once activated by binding to activins, activin receptors, type I recruit and phosphorylate type II receptors, leading to the activation of downstream signaling pathways, including SMAD proteins. Activated SMAD proteins then translocate to the nucleus and regulate gene expression, thereby mediating various cellular responses such as proliferation, differentiation, apoptosis, and migration.

Mutations in activin receptors, type I have been implicated in several human diseases, including cancer, fibrosis, and developmental disorders. Therefore, understanding the structure and function of activin receptors, type I is essential for developing novel therapeutic strategies to treat these diseases.

Bone Morphogenetic Protein 6 (BMP-6) is a member of the transforming growth factor-beta (TGF-β) superfamily of proteins. It plays crucial roles in bone and cartilage formation, as well as in the regulation of iron metabolism. BMP-6 stimulates the differentiation of mesenchymal stem cells into osteoblasts, which are bone-forming cells, and contributes to the maintenance of bone homeostasis. Additionally, BMP-6 is involved in the process of hepcidin regulation, a hormone that controls iron absorption and recycling in the body. Dysregulation of BMP-6 has been implicated in various diseases, including skeletal disorders and iron metabolism-related conditions.

The pulmonary artery is a large blood vessel that carries deoxygenated blood from the right ventricle of the heart to the lungs for oxygenation. It divides into two main branches, the right and left pulmonary arteries, which further divide into smaller vessels called arterioles, and then into a vast network of capillaries in the lungs where gas exchange occurs. The thin walls of these capillaries allow oxygen to diffuse into the blood and carbon dioxide to diffuse out, making the blood oxygen-rich before it is pumped back to the left side of the heart through the pulmonary veins. This process is crucial for maintaining proper oxygenation of the body's tissues and organs.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Transforming Growth Factor-beta (TGF-β) is a type of cytokine, which is a cell signaling protein involved in the regulation of various cellular processes, including cell growth, differentiation, and apoptosis (programmed cell death). TGF-β plays a critical role in embryonic development, tissue homeostasis, and wound healing. It also has been implicated in several pathological conditions such as fibrosis, cancer, and autoimmune diseases.

TGF-β exists in multiple isoforms (TGF-β1, TGF-β2, and TGF-β3) that are produced by many different cell types, including immune cells, epithelial cells, and fibroblasts. The protein is synthesized as a precursor molecule, which is cleaved to release the active TGF-β peptide. Once activated, TGF-β binds to its receptors on the cell surface, leading to the activation of intracellular signaling pathways that regulate gene expression and cell behavior.

In summary, Transforming Growth Factor-beta (TGF-β) is a multifunctional cytokine involved in various cellular processes, including cell growth, differentiation, apoptosis, embryonic development, tissue homeostasis, and wound healing. It has been implicated in several pathological conditions such as fibrosis, cancer, and autoimmune diseases.

Protein-Serine-Threonine Kinases (PSTKs) are a type of protein kinase that catalyzes the transfer of a phosphate group from ATP to the hydroxyl side chains of serine or threonine residues on target proteins. This phosphorylation process plays a crucial role in various cellular signaling pathways, including regulation of metabolism, gene expression, cell cycle progression, and apoptosis. PSTKs are involved in many physiological and pathological processes, and their dysregulation has been implicated in several diseases, such as cancer, diabetes, and neurodegenerative disorders.

Monocrotaline is not a medical condition but a toxic compound that is found in certain plants, including the Crotalaria species (also known as "rattlebox" or "crowtoe"). It has been used in research to create laboratory models of pulmonary hypertension. Ingestion or inhalation of monocrotaline can lead to serious health effects, including lung damage and death.

Therefore, there is no medical definition for 'Monocrotaline' as it is not a disease or condition.

"Bone" is the hard, dense connective tissue that makes up the skeleton of vertebrate animals. It provides support and protection for the body's internal organs, and serves as a attachment site for muscles, tendons, and ligaments. Bone is composed of cells called osteoblasts and osteoclasts, which are responsible for bone formation and resorption, respectively, and an extracellular matrix made up of collagen fibers and mineral crystals.

Bones can be classified into two main types: compact bone and spongy bone. Compact bone is dense and hard, and makes up the outer layer of all bones and the shafts of long bones. Spongy bone is less dense and contains large spaces, and makes up the ends of long bones and the interior of flat and irregular bones.

The human body has 206 bones in total. They can be further classified into five categories based on their shape: long bones, short bones, flat bones, irregular bones, and sesamoid bones.

Bone Morphogenetic Protein 5 (BMP-5) is a growth factor belonging to the Transforming Growth Factor-β (TGF-β) superfamily. It plays crucial roles in bone and cartilage formation during embryonic development, as well as in fracture healing and tissue repair in adults. BMP-5 stimulates the differentiation of mesenchymal stem cells into chondrocytes and osteoblasts, which are essential for the production of cartilage and bone tissues, respectively. Additionally, BMP-5 has been implicated in regulating cell proliferation, apoptosis, and migration during various developmental and repair processes.

Transforming Growth Factor beta (TGF-β) receptors are a group of cell surface receptors that bind to TGF-β ligands and transduce signals into the cell. These receptors play crucial roles in regulating various cellular processes, including cell growth, differentiation, apoptosis, and extracellular matrix production.

There are two types of TGF-β receptors: type I and type II. Type I receptors, also known as activin receptor-like kinases (ALKs), have serine/threonine kinase activity and include ALK1, ALK2, ALK3, ALK4, ALK5, and ALK6. Type II receptors are constitutively active serine/threonine kinases and include TGF-β RII, ActRII, and ActRIIB.

When a TGF-β ligand binds to a type II receptor, it recruits and phosphorylates a type I receptor, which in turn phosphorylates downstream signaling molecules called Smads. Phosphorylated Smads form complexes with co-Smad proteins and translocate to the nucleus, where they regulate gene expression.

Abnormalities in TGF-β signaling have been implicated in various human diseases, including fibrosis, cancer, and autoimmune disorders. Therefore, understanding the mechanisms of TGF-β receptor function is essential for developing therapeutic strategies to target these conditions.

Bone Morphogenetic Protein 3 (BMP-3) is a member of the transforming growth factor-beta (TGF-β) superfamily of proteins. It plays crucial roles in regulating bone and cartilage development, as well as homeostasis. BMP-3 inhibits the differentiation and mineralization of osteoblasts (cells responsible for bone formation), while promoting the differentiation of chondrocytes (cells responsible for cartilage formation). Additionally, BMP-3 has been implicated in wound healing, tissue regeneration, and cancer progression. Genetic variations in the BMP-3 gene have been associated with several skeletal disorders, including osteoporosis and scoliosis.

Cell differentiation is the process by which a less specialized cell, or stem cell, becomes a more specialized cell type with specific functions and structures. This process involves changes in gene expression, which are regulated by various intracellular signaling pathways and transcription factors. Differentiation results in the development of distinct cell types that make up tissues and organs in multicellular organisms. It is a crucial aspect of embryonic development, tissue repair, and maintenance of homeostasis in the body.

Cell surface receptors, also known as membrane receptors, are proteins located on the cell membrane that bind to specific molecules outside the cell, known as ligands. These receptors play a crucial role in signal transduction, which is the process of converting an extracellular signal into an intracellular response.

Cell surface receptors can be classified into several categories based on their structure and mechanism of action, including:

1. Ion channel receptors: These receptors contain a pore that opens to allow ions to flow across the cell membrane when they bind to their ligands. This ion flux can directly activate or inhibit various cellular processes.
2. G protein-coupled receptors (GPCRs): These receptors consist of seven transmembrane domains and are associated with heterotrimeric G proteins that modulate intracellular signaling pathways upon ligand binding.
3. Enzyme-linked receptors: These receptors possess an intrinsic enzymatic activity or are linked to an enzyme, which becomes activated when the receptor binds to its ligand. This activation can lead to the initiation of various signaling cascades within the cell.
4. Receptor tyrosine kinases (RTKs): These receptors contain intracellular tyrosine kinase domains that become activated upon ligand binding, leading to the phosphorylation and activation of downstream signaling molecules.
5. Integrins: These receptors are transmembrane proteins that mediate cell-cell or cell-matrix interactions by binding to extracellular matrix proteins or counter-receptors on adjacent cells. They play essential roles in cell adhesion, migration, and survival.

Cell surface receptors are involved in various physiological processes, including neurotransmission, hormone signaling, immune response, and cell growth and differentiation. Dysregulation of these receptors can contribute to the development of numerous diseases, such as cancer, diabetes, and neurological disorders.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Smad5 protein is a transcription factor that plays a critical role in the intracellular signaling pathway of transforming growth factor-beta (TGF-β) superfamily members. It is a key player in TGF-β-mediated signal transduction, which regulates various cellular processes such as proliferation, differentiation, migration, and apoptosis.

When TGF-β binds to its receptor on the cell surface, it triggers a cascade of phosphorylation events that ultimately lead to the activation of Smad5 protein. Once activated, Smad5 forms a complex with other Smad proteins (Smad4 and Smad2/3) and translocates into the nucleus, where it binds to specific DNA sequences and regulates the expression of target genes involved in various cellular responses.

Dysregulation of the TGF-β signaling pathway and Smad5 protein function has been implicated in several human diseases, including fibrosis, cancer, and autoimmune disorders. Therefore, understanding the role of Smad5 protein in TGF-β signaling is crucial for developing novel therapeutic strategies to treat these conditions.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Bone Morphogenetic Protein 15 (BMP-15) is a growth factor belonging to the transforming growth factor-beta (TGF-β) superfamily. It plays crucial roles in the development and function of the reproductive system, particularly in the ovary. BMP-15 is primarily produced by the oocytes (egg cells) and stimulates the growth and differentiation of granulosa cells, which surround and support the oocytes during follicular development.

BMP-15 has been shown to promote follicular development, increase ovulation rate, and improve embryo quality in various animal models. In humans, mutations in the BMP15 gene have been associated with ovarian dysfunction, including premature ovarian failure and primary ovarian insufficiency. However, the role of BMP-15 in human reproductive physiology is not yet fully understood, and further research is needed to clarify its exact functions and potential clinical applications.

SNARE proteins, which stands for Soluble N-ethylmaleimide sensitive factor Attachment protein REceptor, are a family of small proteins that play a crucial role in the process of membrane fusion in cells. They are essential for various cellular processes such as neurotransmitter release, hormone secretion, and intracellular trafficking.

SNARE proteins are located on both sides of the membranes that are about to fuse, with one set of SNAREs (v-SNAREs) present on the vesicle membrane and the other set (t-SNAREs) present on the target membrane. During membrane fusion, v-SNAREs and t-SNAREs interact to form a tight complex called a SNARE complex, which brings the two membranes into close proximity and facilitates their fusion.

The formation of the SNARE complex is a highly specific process that involves the alignment of specific amino acid sequences on the v-SNARE and t-SNARE proteins. Once formed, the SNARE complex provides the energy required for membrane fusion, and its disassembly is necessary for the completion of the fusion event.

Mutations in SNARE proteins have been implicated in various neurological disorders, including motor neuron disease and epilepsy. Therefore, understanding the structure and function of SNARE proteins is essential for developing therapies for these conditions.

Bone Morphogenetic Protein 1 (BMP-1) is a member of the transforming growth factor-beta (TGF-β) superfamily of proteins, which are signaling molecules involved in various biological processes such as cell growth, differentiation, and development. BMP-1 plays a crucial role in bone and cartilage formation during embryonic development and fracture healing in adults. It is also known to be involved in the regulation of extracellular matrix (ECM) remodeling and tissue homeostasis.

BMP-1 functions by binding to specific receptors on the cell surface, leading to the activation of intracellular signaling pathways that regulate gene expression and cell behavior. BMP-1 is synthesized as a preproprotein and undergoes proteolytic processing to generate the mature, active form of the protein.

Defects in BMP-1 function have been implicated in various human diseases, including skeletal disorders, fibrotic conditions, and cancer. Therefore, understanding the molecular mechanisms underlying BMP-1 signaling is important for developing therapeutic strategies to treat these conditions.

I must clarify that the term "pedigree" is not typically used in medical definitions. Instead, it is often employed in genetics and breeding, where it refers to the recorded ancestry of an individual or a family, tracing the inheritance of specific traits or diseases. In human genetics, a pedigree can help illustrate the pattern of genetic inheritance in families over multiple generations. However, it is not a medical term with a specific clinical definition.

Bone remodeling is the normal and continuous process by which bone tissue is removed from the skeleton (a process called resorption) and new bone tissue is formed (a process called formation). This ongoing cycle allows bones to repair microdamage, adjust their size and shape in response to mechanical stress, and maintain mineral homeostasis. The cells responsible for bone resorption are osteoclasts, while the cells responsible for bone formation are osteoblasts. These two cell types work together to maintain the structural integrity and health of bones throughout an individual's life.

During bone remodeling, the process can be divided into several stages:

1. Activation: The initiation of bone remodeling is triggered by various factors such as microdamage, hormonal changes, or mechanical stress. This leads to the recruitment and activation of osteoclast precursor cells.
2. Resorption: Osteoclasts attach to the bone surface and create a sealed compartment called a resorption lacuna. They then secrete acid and enzymes that dissolve and digest the mineralized matrix, creating pits or cavities on the bone surface. This process helps remove old or damaged bone tissue and releases calcium and phosphate ions into the bloodstream.
3. Reversal: After resorption is complete, the osteoclasts undergo apoptosis (programmed cell death), and mononuclear cells called reversal cells appear on the resorbed surface. These cells prepare the bone surface for the next stage by cleaning up debris and releasing signals that attract osteoblast precursors.
4. Formation: Osteoblasts, derived from mesenchymal stem cells, migrate to the resorbed surface and begin producing a new organic matrix called osteoid. As the osteoid mineralizes, it forms a hard, calcified structure that gradually replaces the resorbed bone tissue. The osteoblasts may become embedded within this newly formed bone as they differentiate into osteocytes, which are mature bone cells responsible for maintaining bone homeostasis and responding to mechanical stress.
5. Mineralization: Over time, the newly formed bone continues to mineralize, becoming stronger and more dense. This process helps maintain the structural integrity of the skeleton and ensures adequate calcium storage.

Throughout this continuous cycle of bone remodeling, hormones, growth factors, and mechanical stress play crucial roles in regulating the balance between resorption and formation. Disruptions to this delicate equilibrium can lead to various bone diseases, such as osteoporosis, where excessive resorption results in weakened bones and increased fracture risk.

Smad6 protein is a negative regulator of the transforming growth factor-beta (TGF-β) signaling pathway. It belongs to the Smad family of proteins, which are intracellular signal transducers and transcriptional modulators that mediate TGF-β superfamily signaling.

Smad6 functions by inhibiting the formation of active Smad complexes and promoting their degradation, thereby preventing the transcription of TGF-β target genes. It also plays a role in regulating other signaling pathways, including bone morphogenetic protein (BMP) and Wnt signaling.

Mutations in the gene that encodes Smad6 have been associated with certain human diseases, such as craniosynostosis and osteochondroma. Additionally, altered expression of Smad6 has been implicated in various pathological conditions, including cancer, fibrosis, and inflammation.

A lung is a pair of spongy, elastic organs in the chest that work together to enable breathing. They are responsible for taking in oxygen and expelling carbon dioxide through the process of respiration. The left lung has two lobes, while the right lung has three lobes. The lungs are protected by the ribcage and are covered by a double-layered membrane called the pleura. The trachea divides into two bronchi, which further divide into smaller bronchioles, leading to millions of tiny air sacs called alveoli, where the exchange of gases occurs.

Smad8 protein, also known as Smad3b or DPC4, is a transcription factor that plays a critical role in the TGF-β (transforming growth factor-beta) signaling pathway. This pathway regulates various cellular processes such as proliferation, differentiation, and apoptosis. Smad8 protein is primarily located in the cytoplasm, but upon activation by TGF-β ligands, it translocates to the nucleus where it binds to DNA and modulates gene expression. Smad8 forms a complex with other Smad proteins (such as Smad4) and regulates the transcription of target genes involved in various cellular responses. Mutations in the Smad8 gene have been associated with certain types of cancer, including colorectal and pancreatic cancers.

Osteogenesis is the process of bone formation or development. It involves the differentiation and maturation of osteoblasts, which are bone-forming cells that synthesize and deposit the organic matrix of bone tissue, composed mainly of type I collagen. This organic matrix later mineralizes to form the inorganic crystalline component of bone, primarily hydroxyapatite.

There are two primary types of osteogenesis: intramembranous and endochondral. Intramembranous osteogenesis occurs directly within connective tissue, where mesenchymal stem cells differentiate into osteoblasts and form bone tissue without an intervening cartilage template. This process is responsible for the formation of flat bones like the skull and clavicles.

Endochondral osteogenesis, on the other hand, involves the initial development of a cartilaginous model or template, which is later replaced by bone tissue. This process forms long bones, such as those in the limbs, and occurs through several stages involving chondrocyte proliferation, hypertrophy, and calcification, followed by invasion of blood vessels and osteoblasts to replace the cartilage with bone tissue.

Abnormalities in osteogenesis can lead to various skeletal disorders and diseases, such as osteogenesis imperfecta (brittle bone disease), achondroplasia (a form of dwarfism), and cleidocranial dysplasia (a disorder affecting skull and collarbone development).

Qa-SNARE proteins, also known as R-SNAREs, are a subgroup of SNARE (Soluble NSF Attachment REceptor) proteins that play a crucial role in intracellular membrane fusion events. These proteins contain a conserved Qa-SNARE domain, which is characterized by the presence of a glutamine (Q) residue at a specific position within the SNARE motif.

Qa-SNAREs are typically located on the vesicle membrane and interact with other SNARE proteins on the target membrane to form a stable complex, known as a SNARE complex. This interaction brings the two membranes into close proximity, allowing for the fusion of the membranes and the release of cargo from the vesicle into the target compartment.

Examples of Qa-SNARE proteins include syntaxin 1, syntaxin 2, syntaxin 3, and syntaxin 4, which are involved in various intracellular trafficking pathways, such as neurotransmitter release, endocytosis, and Golgi transport. Mutations or dysregulation of Qa-SNARE proteins have been implicated in several human diseases, including neurological disorders and cancer.

Growth Differentiation Factor 2 (GDF2), also known as Bone Morphogenetic Protein 9 (BMP9), is a protein that belongs to the transforming growth factor-beta (TGF-β) superfamily. It is a cytokine with important roles in various biological processes, including angiogenesis (the formation of new blood vessels), cardiovascular development, and skeletal muscle regeneration. GDF2/BMP9 is primarily produced by liver cells called hepatocytes and circulates in the bloodstream. It exerts its effects by binding to specific receptors on the cell surface, which triggers intracellular signaling pathways that regulate gene expression and ultimately influence cell behavior.

Osteoblasts are specialized bone-forming cells that are derived from mesenchymal stem cells. They play a crucial role in the process of bone formation and remodeling. Osteoblasts synthesize, secrete, and mineralize the organic matrix of bones, which is mainly composed of type I collagen.

These cells have receptors for various hormones and growth factors that regulate their activity, such as parathyroid hormone, vitamin D, and transforming growth factor-beta. When osteoblasts are not actively producing bone matrix, they can become trapped within the matrix they produce, where they differentiate into osteocytes, which are mature bone cells that play a role in maintaining bone structure and responding to mechanical stress.

Abnormalities in osteoblast function can lead to various bone diseases, such as osteoporosis, osteogenesis imperfecta, and Paget's disease of bone.

Bone regeneration is the biological process of new bone formation that occurs after an injury or removal of a portion of bone. This complex process involves several stages, including inflammation, migration and proliferation of cells, matrix deposition, and mineralization, leading to the restoration of the bone's structure and function.

The main cells involved in bone regeneration are osteoblasts, which produce new bone matrix, and osteoclasts, which resorb damaged or old bone tissue. The process is tightly regulated by various growth factors, hormones, and signaling molecules that promote the recruitment, differentiation, and activity of these cells.

Bone regeneration can occur naturally in response to injury or surgical intervention, such as fracture repair or dental implant placement. However, in some cases, bone regeneration may be impaired due to factors such as age, disease, or trauma, leading to delayed healing or non-union of the bone. In these situations, various strategies and techniques, including the use of bone grafts, scaffolds, and growth factors, can be employed to enhance and support the bone regeneration process.

Bone density refers to the amount of bone mineral content (usually measured in grams) in a given volume of bone (usually measured in cubic centimeters). It is often used as an indicator of bone strength and fracture risk. Bone density is typically measured using dual-energy X-ray absorptiometry (DXA) scans, which provide a T-score that compares the patient's bone density to that of a young adult reference population. A T-score of -1 or above is considered normal, while a T-score between -1 and -2.5 indicates osteopenia (low bone mass), and a T-score below -2.5 indicates osteoporosis (porous bones). Regular exercise, adequate calcium and vitamin D intake, and medication (if necessary) can help maintain or improve bone density and prevent fractures.

Growth differentiation factors (GDFs) are a subfamily of the transforming growth factor-beta (TGF-β) superfamily of cytokines. They play crucial roles in various biological processes, including cell growth, differentiation, and apoptosis. Specifically, GDFs are involved in the development and maintenance of the skeletal, reproductive, and nervous systems. Some members of this family include GDF5, GDF6, and GDF7, which are essential for normal joint formation and cartilage development; GDF8 (also known as myostatin) is a negative regulator of muscle growth; and GDF11 has been implicated in the regulation of neurogenesis and age-related changes.

R-SNARE proteins are a subgroup of SNARE (Soluble N-ethylmaleimide sensitive factor Attachment protein REceptor) proteins that are characterized by the presence of an arginine (R) residue at a specific position in their SNARE motif. The SNARE motif is a conserved region of around 60-70 amino acids that plays a crucial role in mediating membrane fusion events in cells.

R-SNARE proteins are typically located on the target membrane, where they interact with Q-SNARE proteins (which contain a glutamine (Q) residue at the corresponding position) on the vesicle membrane to form a stable complex known as a SNARE complex. The formation of this complex brings the two membranes into close proximity and provides the energy required for their fusion, allowing for the transport of cargo between intracellular compartments or from the outside to the inside of the cell.

R-SNARE proteins are involved in various intracellular trafficking pathways, including endocytosis, exocytosis, and membrane recycling. Mutations in R-SNARE proteins have been implicated in several human diseases, such as neurological disorders and cancer.

Growth Differentiation Factor 5 (GDF5) is a member of the transforming growth factor-beta (TGF-β) superfamily of proteins, which are involved in various developmental processes such as cell growth, differentiation, and migration. GDF5 plays crucial roles in skeletal development, joint formation, and cartilage maintenance. It is a secreted signaling molecule that binds to specific receptors on the cell surface, activating intracellular signaling pathways that regulate gene expression and ultimately influence cell behavior.

GDF5 has been associated with several genetic disorders affecting the musculoskeletal system, such as brachydactyly type C (shortened fingers or toes), Grebe's recessive chondrodysplasia (disproportionate short stature and joint deformities), and Hunter-Thompson syndrome (a rare skeletal disorder characterized by abnormal bone growth, joint laxity, and other features). Additionally, GDF5 has been implicated in osteoarthritis, a degenerative joint disease, due to its role in maintaining cartilage homeostasis.

Developmental gene expression regulation refers to the processes that control the activation or repression of specific genes during embryonic and fetal development. These regulatory mechanisms ensure that genes are expressed at the right time, in the right cells, and at appropriate levels to guide proper growth, differentiation, and morphogenesis of an organism.

Developmental gene expression regulation is a complex and dynamic process involving various molecular players, such as transcription factors, chromatin modifiers, non-coding RNAs, and signaling molecules. These regulators can interact with cis-regulatory elements, like enhancers and promoters, to fine-tune the spatiotemporal patterns of gene expression during development.

Dysregulation of developmental gene expression can lead to various congenital disorders and developmental abnormalities. Therefore, understanding the principles and mechanisms governing developmental gene expression regulation is crucial for uncovering the etiology of developmental diseases and devising potential therapeutic strategies.

Bone development, also known as ossification, is the process by which bone tissue is formed and grows. This complex process involves several different types of cells, including osteoblasts, which produce new bone matrix, and osteoclasts, which break down and resorb existing bone tissue.

There are two main types of bone development: intramembranous and endochondral ossification. Intramembranous ossification occurs when bone tissue forms directly from connective tissue, while endochondral ossification involves the formation of a cartilage model that is later replaced by bone.

During fetal development, most bones develop through endochondral ossification, starting as a cartilage template that is gradually replaced by bone tissue. However, some bones, such as those in the skull and clavicles, develop through intramembranous ossification.

Bone development continues after birth, with new bone tissue being laid down and existing tissue being remodeled throughout life. This ongoing process helps to maintain the strength and integrity of the skeleton, allowing it to adapt to changing mechanical forces and repair any damage that may occur.

Vesicular transport proteins are specialized proteins that play a crucial role in the intracellular trafficking and transportation of various biomolecules, such as proteins and lipids, within eukaryotic cells. These proteins facilitate the formation, movement, and fusion of membrane-bound vesicles, which are small, spherical structures that carry cargo between different cellular compartments or organelles.

There are several types of vesicular transport proteins involved in this process:

1. Coat Proteins (COPs): These proteins form a coat around the vesicle membrane and help shape it into its spherical form during the budding process. They also participate in selecting and sorting cargo for transportation. Two main types of COPs exist: COPI, which is involved in transport between the Golgi apparatus and the endoplasmic reticulum (ER), and COPII, which mediates transport from the ER to the Golgi apparatus.

2. SNARE Proteins: These proteins are responsible for the specific recognition and docking of vesicles with their target membranes. They form complexes that bring the vesicle and target membranes close together, allowing for fusion and the release of cargo into the target organelle. There are two types of SNARE proteins: v-SNAREs (vesicle SNAREs) and t-SNAREs (target SNAREs), which interact to form a stable complex during membrane fusion.

3. Rab GTPases: These proteins act as molecular switches that regulate the recruitment of coat proteins, motor proteins, and SNAREs during vesicle transport. They cycle between an active GTP-bound state and an inactive GDP-bound state, controlling the various stages of vesicular trafficking, such as budding, transport, tethering, and fusion.

4. Tethering Proteins: These proteins help to bridge the gap between vesicles and their target membranes before SNARE-mediated fusion occurs. They play a role in ensuring specificity during vesicle docking and may also contribute to regulating the timing of membrane fusion events.

5. Soluble N-ethylmaleimide-sensitive factor Attachment Protein Receptors (SNAREs): These proteins are involved in intracellular transport, particularly in the trafficking of vesicles between organelles. They consist of a family of coiled-coil domain-containing proteins that form complexes to mediate membrane fusion events.

Overall, these various classes of proteins work together to ensure the specificity and efficiency of vesicular transport in eukaryotic cells. Dysregulation or mutation of these proteins can lead to various diseases, including neurodegenerative disorders and cancer.

Growth Differentiation Factor 9 (GDF9) is a member of the transforming growth factor-beta (TGF-β) superfamily, which plays crucial roles in various biological processes such as cell growth, differentiation, and apoptosis. Specifically, GDF9 is primarily expressed in oocytes and has essential functions during follicular development and ovulation in the ovary. It regulates granulosa cell proliferation, differentiation, and steroidogenesis, contributing to the maintenance of follicular integrity and promoting follicle growth. Additionally, GDF9 is involved in embryonic development and has been implicated in several reproductive disorders when its expression or function is disrupted.

Bone matrix refers to the non-cellular component of bone that provides structural support and functions as a reservoir for minerals, such as calcium and phosphate. It is made up of organic and inorganic components. The organic component consists mainly of type I collagen fibers, which provide flexibility and tensile strength to the bone. The inorganic component is primarily composed of hydroxyapatite crystals, which give bone its hardness and compressive strength. Bone matrix also contains other proteins, growth factors, and signaling molecules that regulate bone formation, remodeling, and repair.

Vesicle-Associated Membrane Protein 2 (VAMP-2), also known as Synaptobrevin-2, is a type of SNARE (Soluble N-ethylmaleimide sensitive factor Attachment protein REceptor) protein found in neurons. It is primarily located on the membranes of synaptic vesicles, which are small membrane-bound compartments that store neurotransmitters in the presynaptic terminal.

VAMP-2 plays a crucial role in the process of synaptic vesicle fusion with the presynaptic plasma membrane during neurotransmitter release. This protein interacts with other SNARE proteins, such as syntaxin and SNAP-25, to form a stable complex that brings the vesicle and plasma membranes into close proximity, allowing for the fusion of the two membranes and subsequent release of neurotransmitters into the synaptic cleft.

Mutations in the VAMP-2 gene have been associated with certain neurological disorders, such as autism spectrum disorder and epilepsy, highlighting its importance in normal neuronal function.

Bone resorption is the process by which bone tissue is broken down and absorbed into the body. It is a normal part of bone remodeling, in which old or damaged bone tissue is removed and new tissue is formed. However, excessive bone resorption can lead to conditions such as osteoporosis, in which bones become weak and fragile due to a loss of density. This process is carried out by cells called osteoclasts, which break down the bone tissue and release minerals such as calcium into the bloodstream.

Carrier proteins, also known as transport proteins, are a type of protein that facilitates the movement of molecules across cell membranes. They are responsible for the selective and active transport of ions, sugars, amino acids, and other molecules from one side of the membrane to the other, against their concentration gradient. This process requires energy, usually in the form of ATP (adenosine triphosphate).

Carrier proteins have a specific binding site for the molecule they transport, and undergo conformational changes upon binding, which allows them to move the molecule across the membrane. Once the molecule has been transported, the carrier protein returns to its original conformation, ready to bind and transport another molecule.

Carrier proteins play a crucial role in maintaining the balance of ions and other molecules inside and outside of cells, and are essential for many physiological processes, including nerve impulse transmission, muscle contraction, and nutrient uptake.

Synaptosomal-associated protein 25 (SNAP-25) is a protein found in the presynaptic membrane of neurons, which plays a crucial role in the process of synaptic transmission. It is a component of the SNARE complex, a group of proteins that facilitate vesicle docking and fusion with the presynaptic membrane during neurotransmitter release. SNAP-25 binds to other SNARE proteins, syntaxin and VAMP (vesicle-associated membrane protein), forming a tight complex that brings the vesicle membrane into close apposition with the presynaptic membrane, allowing for the fusion of the two membranes and the release of neurotransmitters into the synaptic cleft.

Growth Differentiation Factor 6 (GDF6) is a member of the transforming growth factor-beta (TGF-β) superfamily, which plays crucial roles in various biological processes such as cell growth, differentiation, and development. Specifically, GDF6 is involved in the regulation of skeletal development, joint formation, and limb morphogenesis. It has been shown to inhibit chondrogenic differentiation and promote osteogenic differentiation during bone development. Genetic variations in the GDF6 gene have been associated with certain musculoskeletal disorders, such as osteoarthritis and joint laxity.

Activins are a type of protein that belongs to the transforming growth factor-beta (TGF-β) superfamily. They are produced and released by various cells in the body, including those in the ovaries, testes, pituitary gland, and other tissues. Activins play important roles in regulating several biological processes, such as cell growth, differentiation, and apoptosis (programmed cell death).

Activins bind to specific receptors on the surface of cells, leading to the activation of intracellular signaling pathways that control gene expression. They are particularly well-known for their role in reproductive biology, where they help regulate follicle stimulation and hormone production in the ovaries and testes. Activins also have been implicated in various disease processes, including cancer, fibrosis, and inflammation.

There are three main isoforms of activin in humans: activin A, activin B, and inhibin A. While activins and inhibins share similar structures and functions, they have opposite effects on the activity of the pituitary gland. Activins stimulate the production of follicle-stimulating hormone (FSH), while inhibins suppress it. This delicate balance between activins and inhibins helps regulate reproductive function and other physiological processes in the body.

Syntaxin 1 is a specific type of protein called a SNARE (Soluble N-ethylmaleimide sensitive factor Attachment protein REceptor) protein, which plays a crucial role in the process of synaptic vesicle fusion with the presynaptic membrane during neurotransmitter release. This protein is primarily localized to the presynaptic active zone and helps regulate the precise docking and fusion of synaptic vesicles containing neurotransmitters with the presynaptic membrane, enabling rapid and efficient communication between neurons. Syntaxin 1 interacts with other SNARE proteins such as SNAP-25 (Synaptosomal Associated Protein of 25 kDa) and synaptobrevin/VAMP (Vesicle Associated Membrane Protein), forming a stable complex that facilitates membrane fusion. Dysregulation or mutations in syntaxin 1 have been implicated in various neurological disorders, including epilepsy and autism spectrum disorder.

Qb-SNARE proteins are a subclass of SNARE (Soluble N-ethylmaleimide sensitive factor Attachment protein REceptor) proteins that play a crucial role in intracellular membrane fusion events. Specifically, Qb-SNAREs are located on the target membrane and interact with Qa- and Qc-SNAREs on the vesicle membrane to form a stable complex known as a SNARE complex. This interaction brings the two membranes into close proximity, allowing for the fusion of the vesicle and target membranes and the release of cargo from the vesicle into the target compartment.

Examples of Qb-SNARE proteins include syntaxin 6, syntaxin 13, and Vti1a, which are involved in various intracellular trafficking pathways, such as endocytosis, Golgi transport, and autophagy. Mutations or dysfunction in SNARE proteins have been implicated in several human diseases, including neurological disorders and cancer.

Intercellular signaling peptides and proteins are molecules that mediate communication and interaction between different cells in living organisms. They play crucial roles in various biological processes, including cell growth, differentiation, migration, and apoptosis (programmed cell death). These signals can be released into the extracellular space, where they bind to specific receptors on the target cell's surface, triggering intracellular signaling cascades that ultimately lead to a response.

Peptides are short chains of amino acids, while proteins are larger molecules made up of one or more polypeptide chains. Both can function as intercellular signaling molecules by acting as ligands for cell surface receptors or by being cleaved from larger precursor proteins and released into the extracellular space. Examples of intercellular signaling peptides and proteins include growth factors, cytokines, chemokines, hormones, neurotransmitters, and their respective receptors.

These molecules contribute to maintaining homeostasis within an organism by coordinating cellular activities across tissues and organs. Dysregulation of intercellular signaling pathways has been implicated in various diseases, such as cancer, autoimmune disorders, and neurodegenerative conditions. Therefore, understanding the mechanisms underlying intercellular signaling is essential for developing targeted therapies to treat these disorders.

Smad4 protein is a transcription factor that plays a crucial role in the signaling pathways of transforming growth factor-beta (TGF-β), bone morphogenetic proteins (BMPs), and activins. These signaling pathways are involved in various cellular processes, including cell proliferation, differentiation, apoptosis, and migration.

Smad4 is the common mediator of these pathways and forms a complex with Smad2 or Smad3 upon TGF-β/activin stimulation or with Smad1, Smad5, or Smad8 upon BMP stimulation. The resulting complex then translocates to the nucleus, where it regulates gene expression by binding to specific DNA sequences and interacting with other transcription factors.

Smad4 also plays a role in negative feedback regulation of TGF-β signaling by promoting the expression of inhibitory Smads (Smad6 and Smad7), which compete for receptor binding and prevent further signal transduction. Mutations in the Smad4 gene have been associated with various human diseases, including cancer and vascular disorders.

Bone neoplasms are abnormal growths or tumors that develop in the bone. They can be benign (non-cancerous) or malignant (cancerous). Benign bone neoplasms do not spread to other parts of the body and are rarely a threat to life, although they may cause problems if they grow large enough to press on surrounding tissues or cause fractures. Malignant bone neoplasms, on the other hand, can invade and destroy nearby tissue and may spread (metastasize) to other parts of the body.

There are many different types of bone neoplasms, including:

1. Osteochondroma - a benign tumor that develops from cartilage and bone
2. Enchondroma - a benign tumor that forms in the cartilage that lines the inside of the bones
3. Chondrosarcoma - a malignant tumor that develops from cartilage
4. Osteosarcoma - a malignant tumor that develops from bone cells
5. Ewing sarcoma - a malignant tumor that develops in the bones or soft tissues around the bones
6. Giant cell tumor of bone - a benign or occasionally malignant tumor that develops from bone tissue
7. Fibrosarcoma - a malignant tumor that develops from fibrous tissue in the bone

The symptoms of bone neoplasms vary depending on the type, size, and location of the tumor. They may include pain, swelling, stiffness, fractures, or limited mobility. Treatment options depend on the type and stage of the tumor but may include surgery, radiation therapy, chemotherapy, or a combination of these treatments.

Bone marrow is the spongy tissue found inside certain bones in the body, such as the hips, thighs, and vertebrae. It is responsible for producing blood-forming cells, including red blood cells, white blood cells, and platelets. There are two types of bone marrow: red marrow, which is involved in blood cell production, and yellow marrow, which contains fatty tissue.

Red bone marrow contains hematopoietic stem cells, which can differentiate into various types of blood cells. These stem cells continuously divide and mature to produce new blood cells that are released into the circulation. Red blood cells carry oxygen throughout the body, white blood cells help fight infections, and platelets play a crucial role in blood clotting.

Bone marrow also serves as a site for immune cell development and maturation. It contains various types of immune cells, such as lymphocytes, macrophages, and dendritic cells, which help protect the body against infections and diseases.

Abnormalities in bone marrow function can lead to several medical conditions, including anemia, leukopenia, thrombocytopenia, and various types of cancer, such as leukemia and multiple myeloma. Bone marrow aspiration and biopsy are common diagnostic procedures used to evaluate bone marrow health and function.

Bone diseases is a broad term that refers to various medical conditions that affect the bones. These conditions can be categorized into several groups, including:

1. Developmental and congenital bone diseases: These are conditions that affect bone growth and development before or at birth. Examples include osteogenesis imperfecta (brittle bone disease), achondroplasia (dwarfism), and cleidocranial dysostosis.
2. Metabolic bone diseases: These are conditions that affect the body's ability to maintain healthy bones. They are often caused by hormonal imbalances, vitamin deficiencies, or problems with mineral metabolism. Examples include osteoporosis, osteomalacia, and Paget's disease of bone.
3. Inflammatory bone diseases: These are conditions that cause inflammation in the bones. They can be caused by infections, autoimmune disorders, or other medical conditions. Examples include osteomyelitis, rheumatoid arthritis, and ankylosing spondylitis.
4. Degenerative bone diseases: These are conditions that cause the bones to break down over time. They can be caused by aging, injury, or disease. Examples include osteoarthritis, avascular necrosis, and diffuse idiopathic skeletal hyperostosis (DISH).
5. Tumors and cancers of the bone: These are conditions that involve abnormal growths in the bones. They can be benign or malignant. Examples include osteosarcoma, chondrosarcoma, and Ewing sarcoma.
6. Fractures and injuries: While not strictly a "disease," fractures and injuries are common conditions that affect the bones. They can result from trauma, overuse, or weakened bones. Examples include stress fractures, compound fractures, and dislocations.

Overall, bone diseases can cause a wide range of symptoms, including pain, stiffness, deformity, and decreased mobility. Treatment for these conditions varies depending on the specific diagnosis but may include medication, surgery, physical therapy, or lifestyle changes.

Bone marrow cells are the types of cells found within the bone marrow, which is the spongy tissue inside certain bones in the body. The main function of bone marrow is to produce blood cells. There are two types of bone marrow: red and yellow. Red bone marrow is where most blood cell production takes place, while yellow bone marrow serves as a fat storage site.

The three main types of bone marrow cells are:

1. Hematopoietic stem cells (HSCs): These are immature cells that can differentiate into any type of blood cell, including red blood cells, white blood cells, and platelets. They have the ability to self-renew, meaning they can divide and create more hematopoietic stem cells.
2. Red blood cell progenitors: These are immature cells that will develop into mature red blood cells, also known as erythrocytes. Red blood cells carry oxygen from the lungs to the body's tissues and carbon dioxide back to the lungs.
3. Myeloid and lymphoid white blood cell progenitors: These are immature cells that will develop into various types of white blood cells, which play a crucial role in the body's immune system by fighting infections and diseases. Myeloid progenitors give rise to granulocytes (neutrophils, eosinophils, and basophils), monocytes, and megakaryocytes (which eventually become platelets). Lymphoid progenitors differentiate into B cells, T cells, and natural killer (NK) cells.

Bone marrow cells are essential for maintaining a healthy blood cell count and immune system function. Abnormalities in bone marrow cells can lead to various medical conditions, such as anemia, leukopenia, leukocytosis, thrombocytopenia, or thrombocytosis, depending on the specific type of blood cell affected. Additionally, bone marrow cells are often used in transplantation procedures to treat patients with certain types of cancer, such as leukemia and lymphoma, or other hematologic disorders.

In situ hybridization (ISH) is a molecular biology technique used to detect and localize specific nucleic acid sequences, such as DNA or RNA, within cells or tissues. This technique involves the use of a labeled probe that is complementary to the target nucleic acid sequence. The probe can be labeled with various types of markers, including radioisotopes, fluorescent dyes, or enzymes.

During the ISH procedure, the labeled probe is hybridized to the target nucleic acid sequence in situ, meaning that the hybridization occurs within the intact cells or tissues. After washing away unbound probe, the location of the labeled probe can be visualized using various methods depending on the type of label used.

In situ hybridization has a wide range of applications in both research and diagnostic settings, including the detection of gene expression patterns, identification of viral infections, and diagnosis of genetic disorders.

Follistatin is a glycoprotein that is naturally produced in various tissues, including the ovaries, pituitary gland, and skeletal muscle. It plays an essential role in regulating the activity of members of the transforming growth factor-β (TGF-β) superfamily, particularly the bone morphogenetic proteins (BMPs) and activins.

Follistatin binds to these signaling molecules with high affinity, preventing them from interacting with their receptors and thereby inhibiting their downstream signaling pathways. By doing so, follistatin helps regulate processes such as follicle stimulation in the ovaries, neurogenesis, muscle growth, and inflammation.

Increased levels of follistatin have been associated with muscle hypertrophy, while its deficiency can lead to impaired fertility and developmental abnormalities.

"Body patterning" is a general term that refers to the process of forming and organizing various tissues and structures into specific patterns during embryonic development. This complex process involves a variety of molecular mechanisms, including gene expression, cell signaling, and cell-cell interactions. It results in the creation of distinct body regions, such as the head, trunk, and limbs, as well as the organization of internal organs and systems.

In medical terminology, "body patterning" may refer to specific developmental processes or abnormalities related to embryonic development. For example, in genetic disorders such as Poland syndrome or Holt-Oram syndrome, mutations in certain genes can lead to abnormal body patterning, resulting in the absence or underdevelopment of certain muscles, bones, or other structures.

It's important to note that "body patterning" is not a formal medical term with a specific definition, but rather a general concept used in developmental biology and genetics.

In medical and embryological terms, the mesoderm is one of the three primary germ layers in the very early stages of embryonic development. It forms between the ectoderm and endoderm during gastrulation, and it gives rise to a wide variety of cell types, tissues, and organs in the developing embryo.

The mesoderm contributes to the formation of structures such as:

1. The connective tissues (including tendons, ligaments, and most of the bones)
2. Muscular system (skeletal, smooth, and cardiac muscles)
3. Circulatory system (heart, blood vessels, and blood cells)
4. Excretory system (kidneys and associated structures)
5. Reproductive system (gonads, including ovaries and testes)
6. Dermis of the skin
7. Parts of the eye and inner ear
8. Several organs in the urogenital system

Dysfunctions or abnormalities in mesoderm development can lead to various congenital disorders and birth defects, highlighting its importance during embryogenesis.

Proteins are complex, large molecules that play critical roles in the body's functions. They are made up of amino acids, which are organic compounds that are the building blocks of proteins. Proteins are required for the structure, function, and regulation of the body's tissues and organs. They are essential for the growth, repair, and maintenance of body tissues, and they play a crucial role in many biological processes, including metabolism, immune response, and cellular signaling. Proteins can be classified into different types based on their structure and function, such as enzymes, hormones, antibodies, and structural proteins. They are found in various foods, especially animal-derived products like meat, dairy, and eggs, as well as plant-based sources like beans, nuts, and grains.

Munc18 proteins, also known as Sec1/Munc18 (SM) proteins, are a family of conserved cofactor proteins that play a crucial role in the regulation of membrane fusion events in intracellular trafficking. They are essential for the priming and docking steps of vesicle fusion with target membranes, particularly in neurotransmitter release at synapses.

Munc18 proteins have a characteristic three-domain structure: an N-terminal domain that interacts with SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, a central helical domain, and a C-terminal domain. The N-terminal domain of Munc18 proteins binds to the SNARE complex and stabilizes it in a closed conformation, preventing spontaneous fusion of vesicles with target membranes. Upon stimulation, Munc18 proteins undergo conformational changes that allow for the formation of a stable four-helix bundle between the SNARE proteins, leading to membrane fusion.

Mammalian cells express three isoforms of Munc18 proteins: Munc18-1, Munc18-2, and Munc18-3. Munc18-1 is primarily expressed in neurons and plays a critical role in synaptic vesicle exocytosis. Mutations in the gene encoding Munc18-1 have been associated with certain forms of human neurological disorders, such as epilepsy and intellectual disability. Munc18-2 is widely expressed in non-neuronal cells and regulates the fusion of secretory vesicles, while Munc18-3 is primarily expressed in the testis and regulates spermatogenesis.

Activin receptors are a type of serine/threonine kinase receptor that play a crucial role in various biological processes, including cell growth, differentiation, and apoptosis. They are activated by members of the TGF-β (transforming growth factor-beta) superfamily, particularly activins.

There are two main types of activin receptors: ActR-I and ActR-II. ActR-I exists in two isoforms, ALK2 and ALK4, while ActR-II has two isoforms, ActR-IIA and ActR-IIB. Activation of these receptors leads to the phosphorylation of intracellular signaling molecules, which then translocate to the nucleus and regulate gene expression.

Abnormalities in activin receptor function have been implicated in various diseases, including cancer, fibrosis, and developmental disorders. Therefore, activin receptors are an important target for therapeutic intervention in these conditions.

ID-1 (Inhibitor of Differentiation protein 1) is a gene that encodes for a protein involved in cell differentiation, proliferation, and migration. The ID-1 protein belongs to the family of helix-loop-helix proteins, which are transcription factors that regulate gene expression.

ID-1 functions as a dominant negative inhibitor of basic helix-loop-helix (bHLH) transcription factors, which promote cell differentiation and are essential for the development and maintenance of tissues and organs. ID-1 binds to these bHLH factors and prevents them from forming functional complexes with their partner proteins, thereby inhibiting their ability to activate target genes involved in differentiation.

ID-1 is widely expressed during embryonic development and plays critical roles in various biological processes, including neurogenesis, hematopoiesis, and vasculogenesis. In adults, ID-1 expression is usually restricted to stem cells and proliferating cells, where it helps maintain the undifferentiated state and promotes cell proliferation and migration.

Abnormal ID-1 expression has been implicated in several diseases, including cancer, where increased ID-1 levels have been associated with tumor progression, metastasis, and poor clinical outcomes. Therefore, ID-1 is an attractive target for therapeutic intervention in various pathological conditions.

Qa-SNARE and Qb-SNARE proteins are types of SNARE (Soluble NSF Attachment REceptor) proteins that play a crucial role in the process of membrane fusion in eukaryotic cells. Specifically, they are involved in the fusion of vesicles with target membranes during intracellular transport.

Qa-SNARE proteins (also known as R-SNAREs) are located on the vesicle membrane and have a single SNARE domain. Qb-SNARE proteins, on the other hand, are located on the target membrane and have two SNARE domains.

During membrane fusion, a Qa-SNARE protein on the vesicle membrane interacts with a Qbc-SNARE complex (composed of one Qb-SNARE and one Qc-SNARE protein) on the target membrane to form a stable four-helix bundle called a SNARE complex. This interaction brings the two membranes into close proximity, allowing for their fusion and the release of vesicle contents into the target compartment.

Qc-SNARE proteins are also known as syntaxins and play important roles in various cellular processes, including neurotransmitter release, hormone secretion, and intracellular trafficking.

There are four bone morphogenetic protein receptors: Bone morphogenetic protein receptor, type 1: ACVR1 BMPR1A BMPR1B Bone ... Bone morphogenetic protein Miyazono K, Kamiya Y, Morikawa M (January 2010). "Bone morphogenetic protein receptors and signal ... Bone morphogenetic protein receptors are serine-threonine kinase receptors. Transforming growth factor beta family proteins ... morphogenetic protein receptor, type 2 Both type 1 and 2 bone morphogenetic protein receptors have a single transmembrane ...
Bone morphogenetic protein type I receptors are single pass, type I transmembrane proteins. They belong to a class of receptor ... The three types of type I BMP receptors are ACVR1, BMPR1A and BMPR1B. Bone+Morphogenetic+Protein+Receptors,+Type+I at the U.S. ... Receptors, Transmembrane receptors, S/T domain, GS domain, Bone morphogenetic protein, EC 2.7.11, All stub articles, ... serine/threonine kinases that bind members of the TGF beta superfamily of ligands-the bone morphogenetic proteins. ...
BMP4 bone morphogenetic protein 4". Miyazono K, Kamiya Y, Morikawa M (January 2010). "Bone morphogenetic protein receptors and ... type II receptor for bone morphogenetic protein-4 that forms differential heteromeric complexes with bone morphogenetic protein ... Bone morphogenetic protein 4 is a protein that in humans is encoded by BMP4 gene. BMP4 is found on chromosome 14q22-q23. BMP4 ... Bone morphogenetic proteins are known to stimulate bone formation in adult animals. This is thought that inducing osteoblastic ...
Bone morphogenetic protein receptor type-1B also known as CDw293 (cluster of differentiation w293) is a protein that in humans ... Bone morphogenetic protein, Clusters of differentiation, GS domain, Receptors, Transmembrane receptors, S/T domain, EC 2.7.11) ... "Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling". J. Biol. ... "Entrez Gene: bone morphogenetic protein receptor". Mishina Y, Starbuck MW, Gentile MA, Fukuda T, Kasparcova V, Seedor JG, Hanks ...
... and bone morphogenetic protein receptor, type IA. Other LU domain proteins are small globular proteins such as CD59 antigen, ... Three-finger proteins or three-finger protein domains (3FP or TFPD) are a protein superfamily consisting of small, roughly 60- ... Protein articles without symbol, Protein folds, Protein families). ... Many LU domain containing proteins are involved in cholinergic signaling and bind acetylcholine receptors, notably linking ...
... and bone morphogenetic protein receptor, type IA. Other LU domain proteins are small globular proteins such as CD59 antigen, ... Besides uPAR, other receptors with LU domains include members of the transforming growth factor beta receptor (TGF-beta) ... Tsetlin VI (February 2015). "Three-finger snake neurotoxins and Ly6 proteins targeting nicotinic acetylcholine receptors: ... The LU domain (Ly-6 antigen/uPAR) is an evolutionarily conserved protein domain of the three-finger protein superfamily. This ...
... is a bone morphogenetic protein (BMP) co-receptor of the repulsive guidance molecule family. In humans this protein is encoded ... Li J, Ye L, Kynaston HG, Jiang WG (February 2012). "Repulsive guidance molecules, novel bone morphogenetic protein co-receptors ... There is a potential association between RGMs and cancer bone metastasis, as RGMs coordinate bone morphogenetic protein (BMP) ... a bone morphogenetic protein co-receptor". J. Biol. Chem. 280 (14): 14122-9. doi:10.1074/jbc.M410034200. PMID 15671031. Severyn ...
"Enhanced expression of type I receptors for bone morphogenetic proteins during bone formation". J. Bone Miner. Res. 10 (11): ... The bone morphogenetic protein receptor, type IA also known as BMPR1A is a protein which in humans is encoded by the BMPR1A ... "Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling". J. Biol. ... "Entrez Gene: BMPR1A bone morphogenetic protein receptor, type IA". Mishina Y, Starbuck MW, Gentile MA, Fukuda T, Kasparcova V, ...
It is a bone morphogenetic protein receptor, type 1. Activins are dimeric growth and differentiation factors which belong to ... This protein is important in the bone morphogenic protein (BMP) pathway which is responsible for the development and repair of ... receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with cysteine-rich ... and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a ...
"TrkC binds to the bone morphogenetic protein type II receptor to suppress bone morphogenetic protein signaling". Cancer ... Other example of tyrosine kinase receptors include the insulin receptor, the IGF-1 receptor, the MuSK protein receptor, the ... Tropomyosin receptor kinase C (TrkC), also known as NT-3 growth factor receptor, neurotrophic tyrosine kinase receptor type 3, ... Each type of Trk receptor tends to bind specific neurotrophins: TrkA is the receptor for NGF, TrkB the receptor for BDNF and NT ...
Chen AL, Fang C, Liu C, Leslie MP, Chang E, Di Cesare PE (November 2004). "Expression of bone morphogenetic proteins, receptors ... Bone morphogenetic protein 3, also known as osteogenin, is a protein in humans that is encoded by the BMP3 gene. The protein ... It, unlike other bone morphogenetic proteins (BMP's) inhibits the ability of other BMP's to induce bone and cartilage ... "Bone morphogenetic protein-3 is a negative regulator of bone density". Nature Genetics. 27 (1): 84-8. doi:10.1038/83810. PMID ...
BMPs interact with specific receptors on the cell surface, referred to as bone morphogenetic protein receptors (BMPRs). Signal ... Spinal Fusion and Bone Morphogenetic Protein Reddi AH (1997). "Bone morphogenetic proteins: an unconventional approach to ... BMP: The What and the Who BMPedia - the Bone Morphogenetic Protein Wiki Bone+Morphogenetic+Proteins at the U.S. National ... Blázquez-Medela, Ana M.; Jumabay, Medet; Boström, Kristina I. (2019-01-04). "Beyond the bone: Bone morphogenetic protein ...
1995). "Cloning and characterization of a human type II receptor for bone morphogenetic proteins". Proc. Natl. Acad. Sci. U.S.A ... Mitchell PJ, Sara EA, Crompton MR (Oct 2000). "A novel adaptor-like protein which is a substrate for the non-receptor tyrosine ... This gene encodes the substrate of breast tumor kinase, an Src-type non-receptor tyrosine kinase. The encoded protein possesses ... Signal-transducing adaptor protein 2 is a protein that in humans is encoded by the STAP2 gene. ...
... (RGMa) is a bone morphogenetic protein (BMP) co-receptor of the repulsive guidance molecule ... Li J, Ye L, Kynaston HG, Jiang WG (February 2012). "Repulsive guidance molecules, novel bone morphogenetic protein co-receptors ... 2007). "Repulsive guidance molecule RGMa alters utilization of bone morphogenetic protein (BMP) type II receptors by BMP2 and ... All three RGM proteins appear capable of binding selected BMPs (bone morphogenetic proteins). RGMs may play inhibitory roles in ...
"HIV-1 Tat interaction with cyclin T1 represses mannose receptor and the bone morphogenetic protein receptor-2 transcription". ... Jiang C, Ito M, Piening V, Bruck K, Roeder RG, Xiao H (2004). "TIP30 interacts with an estrogen receptor alpha-interacting ... "Entrez Gene: HTATIP2 HIV-1 Tat interactive protein 2, 30kDa". Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to ... King FW, Shtivelman E (2004). "Inhibition of nuclear import by the proapoptotic protein CC3". Mol. Cell. Biol. 24 (16): 7091- ...
"Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel ... The glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family ... Brubaker PL, Drucker DJ (2002). "Structure-function of the glucagon receptor family of G protein-coupled receptors: the ... modifying protein-directed G protein signaling specificity for the calcitonin gene-related peptide family of receptors receptor ...
However it has been demonstrated that hemojuvelin interacts with bone morphogenetic protein (BMP), possibly as a co-receptor, ... Li J, Ye L, Kynaston HG, Jiang WG (February 2012). "Repulsive guidance molecules, novel bone morphogenetic protein co-receptors ... "Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression". Nat. Genet. 38 (5): 531-9. doi:10.1038/ ... In contrast, the membrane-spanning protein, neogenin, a receptor for the related molecule, RGMa, preferentially bound membrane- ...
SMAD1 is a receptor regulated SMAD (R-SMAD) and is activated by bone morphogenetic protein type 1 receptor kinase. GRCm38: ... This protein mediates the signals of the bone morphogenetic proteins (BMPs), which are involved in a range of biological ... this protein can be phosphorylated and activated by the BMP receptor kinase. The phosphorylated form of this protein forms a ... Developmental genes and proteins, MH1 domain, MH2 domain, R-SMAD, Human proteins). ...
SMAD5 is a receptor regulated SMAD (R-SMAD) and is activated by bone morphogenetic protein type 1 receptor kinase. It may play ... Like many other TGFβ family members SMAD5 is involved in cell signalling and modulates signals of bone morphogenetic proteins ( ... Developmental genes and proteins, MH1 domain, MH2 domain, R-SMAD, Transcription factors, Human proteins, All stub articles, ... Mothers against decapentaplegic homolog 5 also known as SMAD5 is a protein that in humans is encoded by the SMAD5 gene. SMAD5, ...
Bone morphogenetic protein receptor type II or BMPR2 is a serine/threonine receptor kinase encoded by the BMPR2 gene. It binds ... Bone morphogenetic protein, Developmental genes and proteins, TS domain, S/T kinase, Receptors, EC 2.7.11). ... BMPR2 is expressed on both human and animal granulosa cells, and is a crucial receptor for bone morphogenetic protein 15 (BMP15 ... Gilboa L, Nohe A, Geissendörfer T, Sebald W, Henis YI, Knaus P (March 2000). "Bone morphogenetic protein receptor complexes on ...
When a bone morphogenetic protein binds to a receptor (BMP type 1 receptor kinase) it causes SMAD9 to interact with SMAD anchor ... SMAD9 is a receptor regulated SMAD (R-SMAD) and is activated by bone morphogenetic protein type 1 receptor kinase. There are ... The SMAD proteins are homologs of both the drosophila protein, mothers against decapentaplegic (MAD) and the C. elegans protein ... Developmental genes and proteins, MH1 domain, MH2 domain, R-SMAD, Transcription factors, Human proteins, All stub articles, ...
The enzyme is implicated in the trafficking and signaling of type I bone morphogenetic protein (BMP) receptors in zebra fish ( ... The gene encodes SPTLC1 protein, which together with SPTLC2 protein, forms serine palmitoyltransferase (SPT) in humans. SPT is ... such as inflammation of the underlying bones, spontaneous bone fractures, and progressive degeneration of weight-bearing joints ... The gene encodes SPTLC2 protein which is one of two subunits of SPT. As mutations in the gene affect the same enzyme as those ...
"Expression of bone morphogenetic proteins (BMP), BMP receptors, and BMP associated proteins in human trabecular meshwork and ... Bone morphogenetic protein 5 is a protein that in humans is encoded by the BMP5 gene. The protein encoded by this gene is ... "Effect of bone morphogenetic proteins-4, -5 and -6 on DNA synthesis and expression of bone-related proteins in cultured human ... Bone morphogenetic proteins are known for their ability to induce bone and cartilage development. BMP5 may play a role in ...
"Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 ... The signaling complex for bone morphogenetic proteins (BMP) start with a ligand binding with a high affinity type I receptor ( ... Growth differentiation factor 2 (GDF2) also known as bone morphogenetic protein (BMP)-9 is a protein that in humans is encoded ... "Autocrine bone morphogenetic protein-9 signals through activin receptor-like kinase-2/Smad1/Smad4 to promote ovarian cancer ...
Gilboa L, Nohe A, Geissendörfer T, Sebald W, Henis YI, Knaus P (March 2000). "Bone morphogenetic protein receptor complexes on ... Bone morphogenetic protein 2 or BMP-2 belongs to the TGF-β superfamily of proteins. BMP-2 like other bone morphogenetic ... Bone morphogenetic protein 2 has been shown to interact with BMPR1A. Bone morphogenetic protein 2 is shown to stimulate the ... As an adjuvant to allograft bone or as a replacement for harvested autograft, bone morphogenetic proteins (BMPs) appear to ...
The BMPs bind to the bone morphogenetic protein receptor type II (BMPR2). Some of the proteins of the BMP family are BMP4 and ... Wnt proteins binds to its transmembrane receptor of the Frizzled family of proteins. The binding of Wnt to a Frizzled protein ... An adaptor protein (such as SOS) recognizes the phosphorylated tyrosine on the receptor. This protein functions as a bridge ... Then active Smoothened protein is able to inhibit PKA and Slimb, so that the Ci protein is not cleaved. This intact Ci protein ...
By occupying type I receptors for Activin and bone morphogenetic protein (BMP), it also plays a role in negative feedback of ... Itoh F, Asao H, Sugamura K, Heldin CH, ten Dijke P, Itoh S (August 2001). "Promoting bone morphogenetic protein signaling ... "Differential inhibition of Smad6 and Smad7 on bone morphogenetic protein- and activin-mediated growth arrest and apoptosis in B ... Mothers against decapentaplegic homolog 7 or SMAD7 is a protein that in humans is encoded by the SMAD7 gene. SMAD7 is a protein ...
"Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel ... The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has three repeats of RRM ... Wada K, Inoue K, Hagiwara M (August 2002). "Identification of methylated proteins by protein arginine N-methyltransferase 1, ... Wada K, Inoue K, Hagiwara M (August 2002). "Identification of methylated proteins by protein arginine N-methyltransferase 1, ...
"Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel ... U7 snRNA-associated Sm-like protein LSm10 is a protein that in humans is encoded by the LSM10 gene. LSM10 has been shown to ... "A novel zinc finger protein is associated with U7 snRNP and interacts with the stem-loop binding protein in the histone pre- ... "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. Bibcode:2005Natur. ...
"Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel ... "Synergistic activation of the insulin gene by a LIM-homeo domain protein and a basic helix-loop-helix protein: building a ... "Transcriptional synergy between LIM-homeodomain proteins and basic helix-loop-helix proteins: the LIM2 domain determines ... LIM homeobox transcription factor 1, alpha, also known as LMX1A, is a protein which in humans is encoded by the LMX1A gene. ...
"Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel ... Nakayama M, Kikuno R, Ohara O (November 2002). "Protein-protein interactions between large proteins: two-hybrid screening using ... DNA topoisomerase 2-binding protein 1 (TOPBP1) is a scaffold protein that in humans is encoded by the TOPBP1 gene. TOPBP1 was ... TOPBP1 was first identified as a DNA damage protein through its association with BRCA1, which is a protein heavily implicated ...
There are four bone morphogenetic protein receptors: Bone morphogenetic protein receptor, type 1: ACVR1 BMPR1A BMPR1B Bone ... Bone morphogenetic protein Miyazono K, Kamiya Y, Morikawa M (January 2010). "Bone morphogenetic protein receptors and signal ... Bone morphogenetic protein receptors are serine-threonine kinase receptors. Transforming growth factor beta family proteins ... morphogenetic protein receptor, type 2 Both type 1 and 2 bone morphogenetic protein receptors have a single transmembrane ...
Sino Biological manufactures a huge range of BMPR proteins for all your research needs. ... family is a group of transmembrane proteins that play crucial roles in cell signaling and development. ... The Bone Morphogenetic Protein Receptor (BMPR) family includes transmembrane receptors that play vital roles in tissue ... analyzed the impact of RN1 (a natural product extracted from Panax notoginseng) on bone morphogenetic protein receptors (BMPR1A ...
Learn about Bone Morphogenetic Protein Receptors at online-medical-dictionary.org ... A family of CELL SURFACE RECEPTORS that bind BONE MORPHOGENETIC PROTEINS. They are PROTEIN-SERINE-THREONINE KINASES that ... Bone Morphogenetic Protein Receptors. Synonyms. BMP Receptor. BMP Receptors. Receptor, BMP. Receptors, BMP. ...
Type-3 metabotropic glutamate receptors negatively modulate bone morphogenetic protein receptor signaling and support the ... The cross-talk between mGlu3 receptors and BMP receptors was mediated by the activation of the mitogen-activated protein kinase ... receptors sustained the undifferentiated state of GICs in culture by negatively modulating the action of bone morphogenetic ... These findings pave the way to a new non-cytotoxic treatment of malignant gliomas based on the use of mGlu3 receptor ...
Bone Morphogenetic Protein Receptors. Dev Dyn 2007 Feb;236(2):502-11 CRIM1 protein, human 0 *Membrane Proteins Bone ... CRIM1 protein, C elegans 0 *Membrane Proteins *Caenorhabditis elegans Proteins Bone Morphogenetic Protein Receptors. Dev Biol ... Definition: A family of CELL SURFACE RECEPTORS that bind BONE MORPHOGENETIC PROTEINS. They are PROTEIN-SERINE-THREONINE KINASES ... that mediate SIGNAL TRANSDUCTION PATHWAYS through SMAD PROTEINS. Examples Bone Morphogenetic Protein Receptors, Type I ...
BMPR1A: bone morphogenetic protein receptor type 1A. *BMPR2: bone morphogenetic protein receptor type 2 ...
SBD in four families caused by mutations in TMEM53 and demonstrate the role this protein plays in BMP signalling during bone ... Sclerosing bone disorder (SBD) includes a broad spectrum of monogenic diseases characterised by increased bone density. Here, ... Its abnormalities manifest themselves in various diseases, including sclerosing bone disorder (SBD). Exploration of genes that ... thus leading to overactivated BMP signaling that promotes bone formation and contributes to the SBD phenotype. Our results ...
bone morphogenetic protein receptor, type 1A; targeted mutation 2.1, Richard R Behringer. ... which encodes roughly a third of the extracellular domain of the receptor within the ligand-binding domain. (J:75074, J:97780) ...
bone morphogenetic protein receptor, type 1B MGI:107191 .yui-skin-sam .yui-dt th{ background:url(https://www.informatics.jax. ...
Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva. J Biol ... Miyazono K, Kamiya Y, Morikawa M. Bone morphogenetic protein receptors and signal transduction. J Biochem. 2010;147(1):35-51. ... Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor ... Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev. 1996;10(13):1580-1594.. View this ...
KBU2046 binds chaperone heterocomplexes, selectively alters binding of client proteins that regulate motility, and lacks all ... They demonstrate its ability to selectively inhibit activation of client proteins that stimulate cell motility. ... Across three different murine models of human prostate and breast cancer, KBU2046 inhibits metastasis, decreases bone ... suppression of prostate cancer invasion is regulated by activin and bone morphogenetic protein type II receptors. PLoS ONE 8, ...
A case of well-documented PVOD associated with a bone morphogenetic protein receptor protein type II (BMPR2) mutation has been ... Pulmonary veno-occlusive disease caused by an inherited mutation in bone morphogenetic protein receptor II. Am J Respir Crit ... 22] PVOD seems to occur more commonly in bone marrow transplant recipients than in the general population. [23, 24] ... Pulmonary veno-occlusive disease in an adult following bone marrow transplantation. Case report and review of the literature. ...
Expression of genes for bone morphogenetic proteins and receptors in human dental pulp. Arch Oral Biol. 1996, 41(10):919-23.. 6 ... Synergistic effects of different bone morphogenetic protein type I receptors on alkaline phosphatase induction. J Cell Sci. ... Growth/differentiation factor-5 (GDF-5) is a member of the bone morphogenetic protein (BMP) family, which is a subgroup of the ... Tsumaki N, Nakase T, Miyaji T, Kakiuchi M, Kimura T, Ochi T, Yoshikawa H. Bone morphogenetic protein signals are required for ...
MADH4 and bone morphogenetic protein receptor 1A (BMPR1A): both are involved in bone morphogenetic protein (BMP) mediated ... A total of 77 JP cases were sequenced for mutations in the MADH4, BMPR1A, BMPR1B, BMPR2, and/or ACVR1 (activin A receptor) ... BMP, bone morphogenetic protein. *BMPR1A, bone morphogenetic protein receptor 1A gene. *CS, Cowden syndrome ... BMP, bone morphogenetic protein. *BMPR1A, bone morphogenetic protein receptor 1A gene. *CS, Cowden syndrome ...
... into Osteoblasts in a Perioxisome Proliferator-Activated Receptor Gamma-Mediated Fashion via Bone Morphogenetic Protein ... into Osteoblasts in a Perioxisome Proliferator-Activated Receptor Gamma-Mediated Fashion via Bone Morphogenetic Protein ... into Osteoblasts in a Perioxisome Proliferator-Activated Receptor Gamma-Mediated Fashion via Bone Morphogenetic Protein ... into Osteoblasts in a Perioxisome Proliferator-Activated Receptor Gamma-Mediated Fashion via Bone Morphogenetic Protein ...
This article is a brief overview of the basic genetics of this strange bone disease that leads to the formation of a second ... The gene is for a receptor called ACVR1 in the bone morphogenetic protein-signalling pathway (BMP). Its situated on chromosome ... And it doesnt help matters if the excess bone is cut away. It just results in an explosion of bone growth in unwanted areas. ... Even bumps and bruises can cause tissue to turn to bone.. Basic genetics of FOP. FOP is an autosomal dominant condition and ...
6 Howe J R, Bair J L, Sayed M G. et al . Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in ... In weiteren 20 % der Fälle lassen sich Mutationen im „bone morphogenic receptor 1A gene" (BMPR1A) nachweisen [6]. Sowohl SMAD4 ...
bone morphogenetic protein receptor, type IA pseudogene. LOC100421775. 100421775. -. 132147124. 132149553. 2429. INFERRED. ... protein tyrosine phosphatase, receptor type, K. RAB32. 10981. 6q24.3. 146864828. 146876086. 11258. PROVISIONAL. RAB32, member ... protein tyrosine phosphatase, non-receptor type 11 pseudogene. LOC644135. 644135. 6q23.3. 136364990. 136393965. 28975. MODEL. ... nuclear receptor coactivator 7. NCRNA00271. 100131814. 6q23.3. 135818939. 136011976. 193037. PREDICTED. non-protein coding RNA ...
Recombinant Human Bone Morphogenetic protein Receptor-1A. 7-00163 CHI Scientific 2µg. Ask for price ... TL-1A interacts with TNFRSF25/DR3 receptor, but can also bind to a decoy receptor TNFRSF21/DR6. Recombinant human TL-1A is a ... Purity: WAP four-disulfide core domain protein 2, Major epididymis-specific protein E4, Putative protease i ... Recombinant Infectious Bovine Rhinotracheitis (IBR or BHV-1/BoHV-1) gB protein control for western blot. ...
An endothelial activin A-bone morphogenetic protein receptor type 2 link is overdriven in pulmonary hypertension. Nat Commun ... including bone morphogenic protein receptor type II, activin receptor type II A (ActRIIA), and the ActRIIA ligands activin A, ... Targeting transforming growth factor-beta receptors in pulmonary hypertension. Eur Respir J 2021; 57: 2002341. doi:10.1183/ ... Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. Eur Respir J ...
... bone morphogenetic protein) signaling on spinal cord development in ... type I receptor serine-threonine kinases) inhibitor, to study the effect of TGFβ1/2/3 (tumor growth factor β) and BMP ( ... Oral administration of a bone morphogenetic protein type I receptor inhibitor prevents the development of anemia of ... bone morphogenetic protein) signaling on spinal cord development in zebrafish.. It has also been used to inhibit SMAD ( ...
Distinct role of type I bone morphogenetic protein receptors in the formation and differentiation of cartilage. Genes Dev. ... Divergent regulation by p44/p42 MAP kinase and p38 MAP kinase of bone morphogenetic protein-4-stimulated osteocalcin synthesis ... the Dach protein functions in the context of the DNA-binding protein Six, highlighting the Dach protein as a potent modulator ... Ski represses bone morphogenic protein signaling in Xenopus and mammalian cells. Proc. Natl. Acad. Sci. USA ...
Bone morphogenetic protein receptor type II or BMPR2 is a serine/threonine receptor kinase. It binds Bone morphogenetic ... Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ... Receptor/signaling modulators. Signaling peptide/protein receptor modulators. Growth factor receptor modulators. Cytokine ... BMPR2 is expressed on both human and animal granulosa cells, and is a crucial receptor for bone morphogenetic protein 15 (BMP15 ...
... is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling. Open Biol 4 ... Transforming Growth Factor β (TGFβ), Bone Morphogenetic Protein (BMP) and Wnt signalling pathways. ... USP15 targets ALK3/BMPR1A for deubiquitylation to enhance bone morphogenetic protein signalling. Open Biol. 4: 140065. ... Affinity-directed PROtein Missile (AdPROM) system (Fulcher et al, 2016) for targeted proteolysis of proteins of interest is an ...
Mishina Y, Suzuki A, Ueno N, Behringer RR (1995) Bmpr encodes a type I bone morphogenetic protein receptor that is essential ... Bone morphogenetic proteins signal through the transforming growth factor-beta type III receptor. J Biol Chem 283(12):7628-7637 ... Distinct spatial and temporal expression patterns of two type I receptors for bone morphogenetic proteins during mouse ... Expression of bone sialoprotein and bone morphogenetic protein-2 in calcific aortic stenosis. J Heart Valve Dis 13(4):560-566 ...
Genetic studies in familial cases of PAH have revealed heterozygous germline mutations in bone morphogenetic protein receptor 2 ... bone morphogenetic protein receptor 2; ECM: extracellular matrix; ET-1: endothelin-1; 5-HT: serotonin; NO: nitric oxide; PGI2: ... In addition to BMPR2, mutations in activin A receptor type II-like 1 (ACVRL1) [51], endoglin (ENG) [52], SMAD family member 9 ( ... NR4A nuclear receptors in atherosclerosis and vein-graft disease. Trends Cardiovasc Med 2007; 17: 105-111. ...
FRET Reveals Novel Protein-Receptor Interaction of Bone Morphogenetic Proteins Receptors and Adaptor Protein 2 at the Cell ... Bone Morphogenetic Protein Receptor Type Ia Localization Causes Increased BMP2 Signaling in Mice Exhibiting Increased Peak Bone ... Altered Plasma Membrane Dynamics of Bone Morphogenetic Protein Receptor Type Ia in a Low Bone Mass Mouse Model ... Casein kinase 2 regulates in vivo bone formation through its interaction with bone morphogenetic protein receptor type Ia ...
A truncated bone morphogenetic protein receptor affects dorsal-ventral patterning in the early Xenopus embryo. Proc. Natl. Acad ... A truncated bone morphogenetic protein receptor affects dorsal-ventral patterning in the early Xenopus embryo. Proc. Natl. Acad ... Bone morphogenetic protein 4, a ventralizing factor in early Xenopus development. Development ... Bone morphogenetic protein 4, a ventralizing factor in early Xenopus development. Development ...
Activin-like kinase type 1 receptor (ALK-1). *. Bone morphogenetic protein receptor type 2 (BMPR2) ... The BMPR2 (bone morphogenic receptor type 2) pathway is targeted by sotatercept, a novel drug. BMPR2 is the most common gene ... Similarly, other protein kinase inhibitors have also been linked to drug-induced pulmonary hypertension (3 Etiology references ... The endothelin pathway is targeted by bosentan, ambrisentan, and macitentan, which are oral endothelin-receptor antagonists ( ...
Mutations in bone morphogenetic protein receptor type 2 (BMPR2) cause familial pulmonary arterial hypertension (FPAH), but the ... by autosomal dominant mutations in the gene encoding bone morphogenetic protein receptor type 2 (BMPR2). However, it is unclear ... Machado RD, Aldred MA, James V, et al. Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension. Hum ... Interestingly, CYP1B1 is transcriptionally activated by oestrogens and oestrogen metabolites, via the oestrogen receptor, to ...
  • There are four bone morphogenetic protein receptors: Bone morphogenetic protein receptor, type 1: ACVR1 BMPR1A BMPR1B Bone morphogenetic protein receptor, type 2 Both type 1 and 2 bone morphogenetic protein receptors have a single transmembrane segment. (wikipedia.org)
  • Type I receptors consist of BMPR1B (ALK6) and BMPR1A (also called ALK3), while type II receptors comprise BMPR2 and ActRII (Activin receptor type II) subtypes. (news-medical.net)
  • BMPR1A and BMPR1B are vital for osteoblast differentiation and chondrogenesis impacting bone remodeling. (news-medical.net)
  • analyzed the impact of RN1 (a natural product extracted from Panax notoginseng ) on bone morphogenetic protein receptors (BMPR1A and BMPR2). (news-medical.net)
  • Recombinant human protein Gal-3, EGFR, BMPR1A, and BMPR2 were obtained from Sino Biological. (news-medical.net)
  • A total of 77 JP cases were sequenced for mutations in the MADH4 , BMPR1A , BMPR1B , BMPR2 , and/or ACVR1 (activin A receptor) genes. (bmj.com)
  • In weiteren 20 % der Fälle lassen sich Mutationen im „bone morphogenic receptor 1A gene" (BMPR1A) nachweisen [ 6 ]. (thieme-connect.de)
  • Bone morphogenetic protein receptor type II or BMPR2 is a serine/threonine receptor kinase . (wikidoc.org)
  • Unlike the TGFβ type II receptor, which has a high affinity for TGF-β1, BMPR2 does not have a high affinity for BMP-2, BMP-7 and BMP-4, unless it is co-expressed with a type I BMP receptor. (wikidoc.org)
  • [1] The low affinity for ligands suggests that BMPR2 may differ from other type II TGF beta receptors in that the ligand may bind the type I receptor first. (wikidoc.org)
  • BMPR2 is expressed on both human and animal granulosa cells, and is a crucial receptor for bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF 9). (wikidoc.org)
  • These two protein signaling molecules and their BMPR2 mediated effects play an important role in follicle development in preparation for ovulation. (wikidoc.org)
  • [3] However, BMPR2 can't bind BMP15 and GDF9 without the assistance of bone morphogenetic protein receptor 1B (BMPR1B) and transforming growth factor β receptor 1 (TGFβR1) respectively. (wikidoc.org)
  • Mutations in bone morphogenetic protein receptor type 2 ( BMPR2 ) cause familial pulmonary arterial hypertension (FPAH), but the penetrance is reduced and females are significantly overrepresented. (ersjournals.com)
  • Familial pulmonary arterial hypertension (FPAH) is caused, in 80% of families, by autosomal dominant mutations in the gene encoding bone morphogenetic protein receptor type 2 ( BMPR2 ). (ersjournals.com)
  • Heritable pulmonary arterial hypertension is associated with several gene mutations, with 75% having a mutation in the bone morphogenetic protein receptor 2 (BMPR2). (biomedcentral.com)
  • As a background, we know that PAH patients have mutations in the bone morphogenetic protein receptor 2, or BMPR2, to which is a member of the TGF-beta superfamily. (reachmd.com)
  • Mutations in bone morphogenetic protein receptor 2 ( BMPR2 ) are the cause of most heritable cases but the vast majority of other cases are genetically undefined. (biomedcentral.com)
  • For example, bone morphogenetic protein receptor type 2 ( BMPR2 ) mutations are observed in 60-80% of familial (FPAH) cases, but data from population registries indicate that penetrance of the disease phenotype ranges from 14 to 42% [ 6 ]. (biomedcentral.com)
  • The Bone Morphogenetic Protein Receptor ( BMPR ) family includes transmembrane receptors that play vital roles in tissue development and cellular signaling. (news-medical.net)
  • Here, we discover a previously unknown type of SBD in four independent families caused by bi-allelic loss-of-function pathogenic variants in TMEM53 , which encodes a nuclear envelope transmembrane protein. (nature.com)
  • In this study, we discover a previously unknown type of SBD and identify its causal gene, TMEM53 , which encodes nuclear envelope transmembrane (NET) protein 53 (TMEM53, also known as NET4). (nature.com)
  • On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. (wikidoc.org)
  • The genetic cause of fibrodysplasia ossificans progressiva lies within the ACVR1 gene, which encodes a type I BMP transmembrane receptor. (medscape.com)
  • The Toll-like receptor (TLR) family in mammals comprises a set of transmembrane proteins characterized by multiple copies of leucine rich repeats in the extracellular domain, and in the IL-1 receptor motif in the cytoplasmic domain. (novusbio.com)
  • Along with other BMPs, including BMP-2, -4 and -7, which are well known as potent osteoinductive growth factors, GDF-5 plays important roles in the development of bones, cartilage and tendons, as evidenced by the tendency for the gene and protein expression levels of GDF-5 to increase over time in these tissues. (ispub.com)
  • The gene is for a receptor called ACVR1 in the bone morphogenetic protein-signalling pathway (BMP). (brighthub.com)
  • Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. (thieme-connect.de)
  • Findings suggest that fibrodysplasia ossificans progressiva maps to band 4q27-31, a region that contains at least 1 gene involved in the bone morphogenic protein (BMP) signaling pathway. (medscape.com)
  • A novel mutation in the activin A type 1 receptor gene was described in one patient. (medscape.com)
  • These findings suggest that GSM-like radiofrequency radiation interferes with gene expression during early gestation and results in aberrations of bone morphogenetic protein expression in the newborn. (greenmedinfo.com)
  • Mutations of this gene introduce a premature stop codon and result in truncated protein versions. (medscape.com)
  • Longevity in untreated congenital growth hormone deficiency due to a homozygous mutation in the GHRH receptor gene. (cdc.gov)
  • Androgen receptor gene CAG repeat polymorphism independently influences recovery of male sexual function after testosterone replacement therapy in postsurgical hypogonadotropic hypogonadism. (cdc.gov)
  • Binding is weak but enhanced by the presence of type I receptors for BMPs. (wikidoc.org)
  • [ 5 ] BMPs are members of the transforming growth factor-beta superfamily and play a role in the development of bone and other tissues. (medscape.com)
  • So we're going to go through its inflammatory modulating effects of what's called BMPs, which I'm going to refer to pretty frequently throughout the presentation, that's called bone morphogenetic proteins. (chiroeco.com)
  • I will go through these BMPs and their stem cell signaling pathway, and then we're going to talk about just principles of bone and cartilage. (chiroeco.com)
  • Recently, a lot of studies have been looking for bone regeneration using BMPs without bone grafts. (bvsalud.org)
  • Bone morphogenetic protein receptors are serine-threonine kinase receptors. (wikipedia.org)
  • The cross-talk between mGlu3 receptors and BMP receptors was mediated by the activation of the mitogen-activated protein kinase pathway. (nih.gov)
  • In vitro analysis reveals that LDN193189 inhibits a number of intracellular kinases such as, mitogen activated protein kinase 14 and 8 ( p38and c-Jun N -terminal kinase respectively), as well as those associated with AKT (serine/threonine kinase) and mTOR (mammalian target of rapamycin) signaling mechanisms. (sigmaaldrich.com)
  • A causative mutation is identified in approximately 97% of patients with definite hereditary hemorrhagic telangiectasia in one of three genes including a mutation in endoglin, a mutation in a locus mapped to chromosome 5, and an activin receptor-like kinase-1 ( ACVRL1 ) mutation that is associated with an increased incidence of primary pulmonary hypertension. (biomedcentral.com)
  • Whereas TGF-b1 may signal via the activin receptor-like kinase (ALK)5 or ALK1 receptors, BMP-9 mainly signals via the ALK1 receptor. (gla.ac.uk)
  • KBU2046 binds chaperone heterocomplexes, selectively alters binding of client proteins that regulate motility, and lacks all the hallmarks of classical chaperone inhibitors, including toxicity. (nature.com)
  • It binds Bone morphogenetic proteins , members of the TGF beta superfamily of ligands, which are involved in paracrine signalling . (wikidoc.org)
  • Remarkably, pharmacological blockade of mGlu3 receptors stimulated the differentiation of cultured GICs into astrocytes, an effect that appeared to be long lasting, independent of the growth conditions, and irreversible. (nih.gov)
  • Growth/differentiation factor-5 (GDF-5) belongs to the bone morphogenetic protein (BMP) family, which is expressed in dental pulp tissues. (ispub.com)
  • Growth/differentiation factor-5 (GDF-5) is a member of the bone morphogenetic protein (BMP) family, which is a subgroup of the transforming growth factor- (TGF-) superfamily. (ispub.com)
  • The differentiation of mesenchymal stem cells towards an osteoblastic fate depends on numerous signaling pathways, including activation of bone morphogenetic protein (BMP) signaling components. (medsci.org)
  • In our previous study, we demonstrated that an agonist of the perioxisome proliferator-activated receptor γ (PPARγ), a master regulator of adipocyte differentiation, stimulates osteoblastic differentiation of cultured human periosteum-derived cells. (medsci.org)
  • It has also been used to inhibit SMAD (homologues of the Drosophila protein, mothers against decapentaplegic), in order to prevent non neuronal differentiation. (sigmaaldrich.com)
  • Prior studies of acute phosphate restriction during the endochondral phase of fracture healing showed delayed chondrocyte differentiation was mechanistically linked to decreased bone morphogenetic protein signaling. (researchgate.net)
  • ALP staining and Alizarin Red S (ARS) staining were used to evaluate osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). (biomedcentral.com)
  • We subsequently discuss how β-TCP can regulate osteogenic processes to aid bone repair/healing, namely osteogenic differentiation of mesenchymal stem cells, formation of blood vessels, release of angiogenic growth factors, and blood clot formation. (frontiersin.org)
  • In particular, he is interested in the role of inflammation on pulmonary vascular remodelling, and the interactions of bone morphogenetic protein receptor II (BMPR II) on other relevant pathways such as the endothelin-1 axis. (imperial.ac.uk)
  • Activation of these receptors sustained the undifferentiated state of GICs in culture by negatively modulating the action of bone morphogenetic proteins, which physiologically signal through the phosphorylation of the transcription factors, Smads. (nih.gov)
  • Binding of BMP2/4 to their receptors initiates the signal transduction cascade by inducing phosphorylation of SMAD1/5/9, which can then form hetero-complexes with SMAD4 followed by translocation into the nucleus to upregulate osteogenesis-related genes. (nature.com)
  • Regulation of proteins through post-translational modifications, including reversible phosphorylation and ubiquitylation. (dundee.ac.uk)
  • They are PROTEIN-SERINE-THREONINE KINASES that mediate SIGNAL TRANSDUCTION PATHWAYS through SMAD PROTEINS . (online-medical-dictionary.org)
  • Mathematical modeling of signal transduction networks has previously been used to map out thermodynamical using rate equations is increasingly attracting attention as a properties of protein-folding models (6,7). (lu.se)
  • Analyses of the molecular pathophysiology using the primary cells from the Tmem53 -/- mice and the TMEM53 knock-out cell lines indicates that TMEM53 inhibits BMP signaling in osteoblast lineage cells by blocking cytoplasm-nucleus translocation of BMP2-activated Smad proteins. (nature.com)
  • The Type I receptor phosphorylates an R-SMAD a transcriptional regulator. (wikidoc.org)
  • Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. (wikidoc.org)
  • Having established PAWS1 as the first non-SMAD substrate of type I BMP receptor (Vogt et al, 2014) , we want to explore whether there are other non-SMAD targets of type I TGFβ and BMP receptors. (dundee.ac.uk)
  • BMP-2 induces chondrocyte proliferation, endochondral bone formation, longitudinal bone growth, and bone and cartilage repair (6, 7). (novusbio.com)
  • The present study it was concluded that the bone morphogenetic protein induces bone neoformation, being an alternative as a substitute to bone grafts and that new carrier discovery is necessary to smooth stability of this carriers in receptor site. (bvsalud.org)
  • We are combining the rapid genome editing capability afforded by CRISPR/Cas9 with advanced knowledge of protein chemistry to engineer robust molecular tools capable of selectively targeting individual proteins for desired functional modulation in cells. (dundee.ac.uk)
  • At that point, given success, Thrasos - which means "boldness" in Greek - could find itself sprinting to the head of the AKI pack, especially if it has the luck to lure a pharma player of the Novartis or Abbott caliber to continue work with THR-184, a small peptide that selectively activates certain receptors of bone morphogenetic proteins. (bioworld.com)
  • We have found that GICs express mGlu3 metabotropic glutamate receptors. (nih.gov)
  • LDN193189 hydrochloride has been used as an ALK2/3 (type I receptor serine-threonine kinases) inhibitor, to study the effect of TGFβ1/2/3 (tumor growth factor β) and BMP (bone morphogenetic protein) signaling on spinal cord development in zebrafish. (sigmaaldrich.com)
  • LDN193189 is a derivative of dorsomorphin that is a highly selective antagonist of BMP receptor isotypes ALK2 and ALK3 (IC 50 of: 5 and 30 nM). (sigmaaldrich.com)
  • The selectivity of LDN193189 for ALK2/3 is 200 fold over the TGF-B type receptors ALK4,-5 and -7. (sigmaaldrich.com)
  • A crosslinking study revealed that recombinant human (rh) BMP-9 bound to ALK1, ALK2, bone morphogenetic protein receptor (BMPR)2, ACVR2A/B and endoglin on primary HSVSMCs. (gla.ac.uk)
  • and this leads to the ACVR1 protein being incorrectly made. (brighthub.com)
  • A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. (medscape.com)
  • Induced EndoMT cells exhibited up-regulation of mesenchymal markers, including collagen type I and α-smooth muscle actin, and a reduction in endothelial cell and junctional proteins, including von Willebrand factor, CD31, occludin, and vascular endothelial-cadherin. (surrey.ac.uk)
  • In addition, he is Principal Investigator for a national, multi-centred, DBPC study investigating the role of an endothelin receptor antagonist, bosentan, in the treatment of pulmonary hypertension associated with interstitial lung disease (B-PHIT-1). (imperial.ac.uk)
  • In addition, development and genetic studies have shown that GDF-5 null mutation or transgenic mice exhibit abnormal growth patterns or overgrowth of limbs, long bones, cartilage, joints and digits (Storm et al. (ispub.com)
  • Mutation analysis of inhibitory guanine nucleotide binding protein alpha (GNAI) loci in young and familial pituitary adenomas. (cdc.gov)
  • Transforming Growth Factor β (TGFβ), Bone Morphogenetic Protein (BMP) and Wnt signalling pathways. (dundee.ac.uk)
  • In fact, crosstalk between two of those pathways-those governed by proteins known as Notch and BMP (for Bone Morphogenetic Protein) receptors-occurs over and over in processes as diverse as forming a tooth, sculpting a heart valve and building a brain. (stowers.org)
  • Expression of both ENG (encoding endoglin) mRNA and protein were heterogeneously upregulated in OS5Ks, and the endoglin-positive (ENG + ) population exhibited growth dependency on endoglin in anchorage-independent cultures. (nih.gov)
  • Despite the function of endoglin as a type III receptor, transforming growth factor β and bone morphogenetic protein-9 signaling were unlikely to contribute to the proliferative phenotype. (nih.gov)
  • Exploration of genes that cause SBD has significantly improved our understanding of the mechanisms that regulate bone formation. (nature.com)
  • The candidate genes exhibit expression patterns in lung and heart similar to that of known PAH risk genes, and most variants occur in conserved protein domains. (biomedcentral.com)
  • Such receptors exhibit unique ligand-binding specificities and mediate distinct signaling cascades, even though they could cross-interact with other TGF-β family ligands. (news-medical.net)
  • BMPR family of proteins is a valuable tool for studying ligand-receptor interactions, downstream signaling events, and determining therapeutic targets. (news-medical.net)
  • Cre-mediated recombination in vivo under the control of a CMV promoter excised the neo cassette in the germline, leaving single loxP sites flanking exon 2, which encodes roughly a third of the extracellular domain of the receptor within the ligand-binding domain. (jax.org)
  • [1] In TGF beta signaling all of the receptors exist in homodimers before ligand binding. (wikidoc.org)
  • In the case of BMP receptors only a small fraction of the receptors exist in homomeric forms before ligand binding. (wikidoc.org)
  • Once a ligand has bound to a receptor, the amount of homomeric receptor oligomers increase, suggesting that the equilibrium shifts towards the homodimeric form. (wikidoc.org)
  • Since BMP-9 signals via the ALK1 receptor, it may be speculated that this ligand acts as a pathogenic mediator of NF. (gla.ac.uk)
  • In in vivo experiments, a 3-month treatment with the brain-permeant mGlu receptor antagonist, LY341495 limited the growth of infiltrating brain tumours originating from GICs implanted into the brain parenchyma of nude mice. (nih.gov)
  • Transforming growth factor beta family proteins bind to these receptors. (wikipedia.org)
  • Transforming growth factor (TGF)-b1 and bone morphogenetic protein (BMP)-9 are both pleiotropic growth factors which are members of TGF-b superfamily. (gla.ac.uk)
  • A cardiomelic developmental field has also been postulated to relate the genetic heterogeneity of HOS (and other similar syndromes) to a cascade of molecules, including the brachyury, sonic hedgehog, bone morphogenetic protein, retinoic acid receptor, and transforming growth factor beta families. (medscape.com)
  • HNP (seen in the image below) is defined as localized displacement of nucleus, cartilage, fragmented apophyseal bone, or fragmented anular tissue beyond the intervertebral disc space. (medscape.com)
  • BMP-2 signals through heterodimeric complexes composed of a type I receptor (Activin RI, BMPR‑IA, or BMPR‑IB) and a type II receptor (BMP RII or Activin RIIB) (2, 5). (novusbio.com)
  • We identified protein-coding variants and performed rare variant association analyses in unrelated participants of European ancestry, including 1647 IPAH cases and 18,819 controls. (biomedcentral.com)
  • Genetic analyses of bone morphogenetic protein 2, 4 and 7 in congenital combined pituitary hormone deficiency. (cdc.gov)
  • It just results in an explosion of bone growth in unwanted areas. (brighthub.com)
  • The main challenge for large bone defect repair and regeneration remains the inadequate recruitment of mesenchymal stem cells (MSCs), reduced vascularization, and decreased growth factors stimulation within the scaffold construct to support cell viability and tissue growth. (frontiersin.org)
  • Consequently, enhancing the adhesion of MSCs, augmenting the release of growth factors, and promoting angiogenic potential of biomaterial scaffolds after implantation are pivotal for successful bone regeneration. (frontiersin.org)
  • To create a favorable osteogenic environment, β-TCP scaffolds have been modified in a number of ways to boost bone healing, including modulating physical features (e.g., pore sizes, porosity and surface roughness), combining with ionic components, and the addition/delivery of growth factors. (frontiersin.org)
  • The redox potential of the cytosolic compartment of the intracellular environment limits disulfide bond formation, whereas the oxidizing extracellular environment contains proteins rich in disulfide bonds. (go.jp)
  • If not for an extracellular antioxidant system to eliminate reactive oxygen and nitrogen species, lipid peroxidation and protein oxidation would become excessive, resulting in cellular damage. (go.jp)
  • Patients with the rare genetic disorder FOP have bones growing in their muscles, ligaments, tendons and other tissues. (brighthub.com)
  • Since the transcriptome is a representation of the phenome, we hypothesized that both sex and sex specific temporal, transcriptomic differences in bone tissues over an 18‐month period would be informative to the underlying molecular proce. (researchgate.net)
  • We aimed to figure out whether exosomes and exosomal miRNA from necrotic bone tissues of patients with NONFH are involved in the pathogenesis of NONFH and reveal the underlying mechanisms. (biomedcentral.com)
  • Therefore, we wondered whether necrotic bone tissues release some signals to impair the self-repair of BMSCs and VECs. (biomedcentral.com)
  • However, no previous study has reported the effect of exosomes from necrotic bone tissues (NONFH exosomes) on the pathogenesis of NONFH. (biomedcentral.com)
  • both are involved in bone morphogenetic protein (BMP) mediated signalling and are members of the TGF-β superfamily. (bmj.com)
  • Bone morphogenetic protein 2 (BMP-2) is a member of the BMP subgroup of the TGF-beta superfamily. (novusbio.com)
  • The expression of Prx1 has been used as a marker to define the skeletal stem cells (SSCs) populations found within the bone marrow and periosteum that contribute to bone regeneration. (researchgate.net)
  • Today's webinar, "Breakthrough in Stem Cell Activation: The First Oral Protein Complex for Tissue Regeneration. (chiroeco.com)
  • It plays a dominant role in embryonic dorsal-ventral patterning, organogenesis, limb bud formation, and bone formation and regeneration (1, 2). (novusbio.com)
  • By way of this review, a deeper understanding of the basic mechanisms of β-TCP for bone repair will be achieved which will aid in the optimization of strategies to promote bone repair and regeneration. (frontiersin.org)
  • Large bone loss as a result of trauma, tumor removal, infection, and developmental congenital disorders, often leads to delayed healing or non-union, and remains a critical challenge for orthopedic surgeons. (frontiersin.org)
  • XIAP, X-linked mammalian inhibitor of apoptosis protein. (rupress.org)
  • The X-linked mammalian inhibitor of apoptosis protein (XIAP) has been shown to bind several partners. (rupress.org)
  • The BMPR family includes both type I and type II receptors. (news-medical.net)
  • A family of CELL SURFACE RECEPTORS that bind BONE MORPHOGENETIC PROTEINS . (online-medical-dictionary.org)
  • PAWS1 and the FAM83 family of uncharacterised proteins. (dundee.ac.uk)
  • PAWS1 is a member of the poorly characterised FAM83 family of proteins that are linked through the conserved DUF1669 domain of unknown function, which possesses a pseudo-Phospholipase D catalytic motif. (dundee.ac.uk)
  • We aim to understand how the DUF1669 domain controls the function of the FAM83 family of proteins in their potentially diverse cellular roles. (dundee.ac.uk)
  • Relative expression and localization of bone morphogenetic proteins (BMP) and their receptors (BMPR), members of a molecular family currently considered as major endocrine and autocrine morphogens and known to be involved in renal development, were investigated in newborn kidneys from RFR exposed and sham irradiated (control) rats. (greenmedinfo.com)
  • That work, published in this week's online issue of PNAS , uses mouse genetics to demonstrate how one Notch family protein, Notch2, shapes an eye structure known as the ciliary body (CB), most likely by ensuring that BMP signals remain loud and clear. (stowers.org)
  • Given the BMPR family's considerable involvement in several diseases, targeting these receptors presents a hopeful avenue for therapeutic interventions. (news-medical.net)
  • Its abnormalities manifest themselves in various diseases, including sclerosing bone disorder (SBD). (nature.com)
  • Sclerosing bone disorder (SBD) is a heterogeneous group of monogenic diseases characterized by increased bone density. (nature.com)
  • BMP proteins are involved in the embryonic development of the skeleton as well as post-natal repair. (brighthub.com)
  • Our results establish a previously unreported SBD entity (craniotubular dysplasia, Ikegawa type) and contribute to a better understanding of the regulation of BMP signaling and bone formation. (nature.com)
  • One of the key discoveries we have made in the lab is the identification of a previously uncharacterised SMAD1-interacting protein FAM83G, which we have termed PAWS1 (Protein Associated With SMAD1) (Vogt et al, 2014) . (dundee.ac.uk)
  • To determine which of these interactions are required for it to inhibit apoptosis, we generated point mutant XIAP proteins and correlated their ability to bind other proteins with their ability to inhibit apoptosis. (rupress.org)
  • Across three different murine models of human prostate and breast cancer, KBU2046 inhibits metastasis, decreases bone destruction, and prolongs survival at nanomolar blood concentrations after oral administration. (nature.com)
  • Efficacy of KBU2046 is demonstrated across several different in vitro models and across multiple murine models of human cancer metastasis, which includes decreased metastasis, decreased bone destruction, and prolonged survival. (nature.com)
  • So sotatercept is a novel first-in-class fusion protein of human activin receptor type IIa, which is fused to the Fc domain of human IgG1. (reachmd.com)
  • Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors. (novusbio.com)
  • Chapter 55: Bone morphogenetic protein receptors and actions. (wikipedia.org)