Latent TGF-beta Binding Proteins
Transforming Growth Factor beta
A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.
beta Karyopherins
Nucleocytoplasmic transport molecules that bind to ALPHA KARYOPHERINS in the CYTOSOL and are involved in transport of molecules through the NUCLEAR PORE COMPLEX. Once inside the CELL NUCLEUS beta karyopherins interact with RAN GTP-BINDING PROTEIN and dissociate from alpha karyopherins. Beta karyopherins bound to RAN GTP-BINDING PROTEIN are then re-transported to the cytoplasm where hydrolysis of the GTP of RAN GTP-BINDING PROTEIN causes release of karyopherin beta.
Protein Binding
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Carrier Proteins
Binding Sites
Amino Acid Sequence
Aggregating human platelets stimulate expression of vascular endothelial growth factor in cultured vascular smooth muscle cells through a synergistic effect of transforming growth factor-beta(1) and platelet-derived growth factor(AB). (1/158)
BACKGROUND: Vascular endothelial growth factor (VEGF), an endothelial mitogen and chemoattractant, has been implicated in the recovery of the endothelium after balloon injury. The increased expression of VEGF in vascular smooth muscle cells (SMC) at sites of injury suggests that this cell type may be a major cellular source of VEGF. This study examined whether aggregating platelets stimulate VEGF expression in cultured SMC. METHODS AND RESULTS: ++VEGF expression in SMC was assessed by Northern blot analysis and by reverse transcription followed by polymerase chain reaction and the release of VEGF by Western blot analysis and immunoassay. Platelet-derived products (PDP) released by aggregating human platelets time-dependently and concentration-dependently enhanced VEGF mRNA levels, mainly that coding for the soluble splice variant VEGF(165/164), and stimulated the release of VEGF protein. These effects were potentiated by transient acidification of PDP, which release bioactive transforming growth factor (TGF)-beta(1), and mimicked by platelet-derived growth factor (PDGF)(AB) and TGF-beta(1) in a synergistic manner. Both a TGF-beta-neutralizing antibody and a PDGF-neutralizing antibody significantly attenuated the effect of acidified PDP on VEGF production. CONCLUSIONS: Aggregating human platelets induce VEGF mRNA expression in cultured SMC and the subsequent release of VEGF protein. This effect can be attributed to a supra-additive action of PDGF(AB) and TGF-beta(1) and may represent a novel mechanism by which platelets contribute to the recovery of the endothelial lining at sites of balloon-injured arteries. (+info)Independent promoters regulate the expression of two amino terminally distinct forms of latent transforming growth factor-beta binding protein-1 (LTBP-1) in a cell type-specific manner. (2/158)
Latent transforming growth factor-beta (TGF-beta)-binding proteins (LTBPs) are components of the extracellular matrix and large latent TGF-beta complexes are secreted by various cells. Human LTBP-1 is known to exist in different forms. LTBP-1L (long) has an amino-terminal extension, which is not found in the smaller LTBP-1S isoform. To study the formation and transcriptional regulation of LTBP-1S and LTBP-1L isoforms, we determined the nucleotide sequences of their 5'-flanking regions. The upstream regions of both isoforms are devoid of TATA boxes but contain other putative binding sites for several transcription factors. Genomic sequencing revealed that LTBP-1L transcript is alternatively spliced to an internal splice acceptor inside exon 1 of LTBP-1S and thus defined the genomic organization of the isoforms. Reporter gene analysis of upstream regions indicated the presence of independent, functional promoters, which regulate the transcription of the isoforms by cell-specific manner. Deletion analyses of the promoter regions revealed specific elements modulating their basal and cell type-specific expression. In SV-40 virus-transformed WI-38 lung fibroblasts a regulatory element repressed the transcription of LTBP-1S by a cell-specific manner. In amniotic epithelial cells, transcription of the LTBP-1S reporter gene construct was down-regulated by a distal upstream element. mRNA levels of the isoforms of LTBP-1 were stimulated in response to TGF-beta1 in WI-38 cells. However, since TGF-beta1 failed to stimulate the transcription of LTBP-1 reporter gene constructs, TGF-beta1 may mediate the induction of the isoforms by post-transcriptional mechanisms. Chromosomal localization of the LTBP-1 gene was refined to 2p22-24. (+info)Developmental expression of latent transforming growth factor beta binding protein 2 and its requirement early in mouse development. (3/158)
Latent transforming growth factor beta (TGF-beta) binding protein 2 (LTBP-2) is an integral component of elastin-containing microfibrils. We studied the expression of LTBP-2 in the developing mouse and rat by in situ hybridization, using tropoelastin expression as a marker of tissues participating in elastic fiber formation. LTBP-2 colocalized with tropoelastin within the perichondrium, lung, dermis, large arterial vessels, epicardium, pericardium, and heart valves at various stages of rodent embryonic development. Both LTBP-2 and tropoelastin expression were seen throughout the lung parenchyma and within the cortex of the spleen in the young adult mouse. In the testes, LTBP-2 expression was seen within lumenal cells of the epididymis in the absence of tropoelastin. Collectively, these results imply that LTBP-2 plays a structural role within elastic fibers in most cases. To investigate its importance in development, mice with a targeted disruption of the Ltbp2 gene were generated. Ltbp2(-/-) mice die between embryonic day 3.5 (E3.5) and E6.5. LTBP-2 expression was not detected by in situ hybridization in E6.5 embryos but was detected in E3.5 blastocysts by reverse transcription-PCR. These results are not consistent with the phenotypes of TGF-beta knockout mice or mice with knockouts of other elastic fiber proteins, implying that LTBP-2 performs a yet undiscovered function in early development, perhaps in implantation. (+info)Specific sequence motif of 8-Cys repeats of TGF-beta binding proteins, LTBPs, creates a hydrophobic interaction surface for binding of small latent TGF-beta. (4/158)
Transforming growth factor (TGF)-betas are secreted in large latent complexes consisting of TGF-beta, its N-terminal latency-associated peptide (LAP) propeptide, and latent TGF-beta binding protein (LTBP). LTBPs are required for secretion and subsequent deposition of TGF-beta into the extracellular matrix. TGF-beta1 associates with the 3(rd) 8-Cys repeat of LTBP-1 by LAP. All LTBPs, as well as fibrillins, contain multiple 8-Cys repeats. We analyzed the abilities of fibrillins and LTBPs to bind latent TGF-beta by their 8-Cys repeats. 8-Cys repeat was found to interact with TGF-beta1*LAP by direct cysteine bridging. LTBP-1 and LTBP-3 bound efficiently all TGF-beta isoforms, LTBP-4 had a much weaker binding capacity, whereas LTBP-2 as well as fibrillins -1 and -2 were negative. A short, specific TGF-beta binding motif was identified in the TGF-beta binding 8-Cys repeats. Deletion of this motif in the 3(rd) 8-Cys repeat of LTBP-1 resulted in loss of TGF-beta*LAP binding ability, while its inclusion in non-TGF-beta binding 3(rd) 8-Cys repeat of LTBP-2 resulted in TGF-beta binding. Molecular modeling of the 8-Cys repeats revealed a hydrophobic interaction surface and lack of three stabilizing hydrogen bonds introduced by the TGF-beta binding motif necessary for the formation of the TGF-beta*LAP - 8-Cys repeat complex inside the cells. (+info)Differential expression of fibromodulin, a transforming growth factor-beta modulator, in fetal skin development and scarless repair. (5/158)
Transforming growth factor-beta (TGF-beta1, -beta2, and -beta3) has been implicated in the ontogenetic transition from scarless fetal repair to adult repair with scar. Generally, TGF-beta exerts its effects through type I and II receptors; however, TGF-beta modulators such as latent TGF-beta binding protein-1 (LTBP-1), decorin, biglycan, and fibromodulin can bind and potentially inhibit TGF-beta activity. To more fully explore the role of TGF-beta ligands, receptors, and potential modulators during skin development and wound healing, we have used a rat model that transitions from scarless fetal-type repair to adult-type repair with scar between days 16 and 18 of gestation. We showed that TGF-beta ligand and receptor mRNA levels did not increase during the transition to adult-type repair in fetal skin, whereas LTBP-1 and fibromodulin expression decreased. In addition, TGF-beta1 and -beta3; type I, II, and III receptors; as well as LTBP-1, decorin, and biglycan were up-regulated during adult wound healing. In marked contrast, fibromodulin expression was initially down-regulated in adult repair. Immunostaining demonstrated significant fibromodulin induction 36 hours after injury in gestation day 16, but not day 19, fetal wounds. This inverse relationship between fibromodulin expression and scarring in both fetal and adult rat wound repair suggests that fibromodulin may be a biologically relevant modulator of TGF-beta activity during scar formation. (+info)Elastic fiber proteins in the glomerular mesangium in vivo and in cell culture. (6/158)
BACKGROUND: Glomerular capillaries of the mammalian kidney are exposed to high intraluminal hydrostatic pressures and require elastic constraint to maintain size, shape, and integrity. Previous morphological and functional studies indicated that the extracellular matrices of glomeruli, that is, basement membrane and mesangial matrix, contribute to glomerular resilience and mechanical stability. Immunofluorescence microscopy findings demonstrated elastic fiber components to be located in the renal vasculature, including glomeruli. The aim of this study was to clarify the exact glomerular localization, composition, and cellular production of these proteins. METHODS: We examined the renal distribution of the elastic fiber proteins fibrillin-1, emilin, microfibril-associated glycoproteins (MAGPs) 1 and 2, latent transforming growth factor-binding protein-1 (LTBP-1), and elastin using immunohistology and immunoelectron microscopy of human, rat, and mouse kidneys. In mesangial cell cultures, we also studied the expression and extracellular deposition of such proteins by use of Northern blotting and immunocytochemistry. RESULTS: Fibrillin-1, emilin, MAGPs 1 and 2, and LTBP-1 were present in glomeruli of mouse, rat, and human kidney, where they were located predominantly in the mesangial extracellular matrix underlying glomerular endothelium and basement membrane. Several of these proteins, as well as elastin, were also expressed in the renal vasculature. While elastin localized to the glomerular vascular pole in afferent and efferent arterioles extending to Bowman's capsule, it was not found in the glomerular capillary tuft. Cultured mesangial cells of rat, mouse, and human kidneys expressed mRNAs of fibrillin-1, emilin, MAGP-2, and elastin, and the respective proteins localized within and outside of mesangial cells, as shown by immunocytochemistry. mRNA expression of fibrillin-1, emilin, and elastin was strong in quiescent mesangial cells; their gene expression was further up-regulated by transforming growth factor-beta1, while it was transiently reduced when cells were exposed to mitogenic 10% fetal calf serum and platelet-derived growth factor. CONCLUSIONS: These findings demonstrate that specific elastic fiber proteins are produced and secreted by mesangial cells. This process is regulated by growth factors. Their abundance in the extracellular matrix of the mesangium is in keeping with the concept that elastic fiber proteins contribute to the mechanical stability and elastic strength of the glomerular capillary tuft. (+info)The latent transforming growth factor-beta-binding protein-1 promotes in vitro differentiation of embryonic stem cells into endothelium. (7/158)
The latent transforming growth factor-beta-binding protein-1 (LTBP-1) belongs to a family of extracellular glycoproteins that includes three additional isoforms (LTBP-2, -3, and -4) and the matrix proteins fibrillin-1 and -2. Originally described as a TGF-beta-masking protein, LTBP-1 is involved both in the sequestration of latent TGF-beta in the extracellular matrix and the regulation of its activation in the extracellular environment. Whereas the expression of LTBP-1 has been analyzed in normal and malignant cells and rodent and human tissues, little is known about LTBP-1 in embryonic development. To address this question, we used murine embryonic stem (ES) cells to analyze the appearance and role of LTBP-1 during ES cell differentiation. In vitro, ES cells aggregate to form embryoid bodies (EBs), which differentiate into multiple cell lineages. We analyzed LTBP-1 gene expression and LTBP-1 fiber appearance with respect to the emergence and distribution of cell types in differentiating EBs. LTBP-1 expression increased during the first 12 d in culture, appeared to remain constant between d 12 and 24, and declined thereafter. By immunostaining, fibrillar LTBP-1 was observed in those regions of the culture containing endothelial, smooth muscle, and epithelial cells. We found that inclusion of a polyclonal antibody to LTBP-1 during EB differentiation suppressed the expression of the endothelial specific genes ICAM-2 and von Willebrand factor and delayed the organization of differentiated endothelial cells into cord-like structures within the growing EBs. The same effect was observed when cultures were treated with either antibodies to TGF-beta or the latency associated peptide, which neutralize TGF-beta. Conversely, the organization of endothelial cells was enhanced by incubation with TGF-beta 1. These results suggest that during differentiation of ES cells LTBP-1 facilitates endothelial cell organization via a TGF-beta-dependent mechanism. (+info)The latent transforming growth factor beta binding protein (LTBP) family. (8/158)
The transforming growth factor beta (TGFbeta) cytokines are a multi-functional family that exert a wide variety of effects on both normal and transformed mammalian cells. The secretion and activation of TGFbetas is regulated by their association with latency-associated proteins and latent TGFbeta binding proteins (LTBPs). Over the past few years, three members of the LTBP family have been identified, in addition to the protoype LTBP1 first sequenced in 1990. Three of the LTBP family are expressed in a variety of isoforms as a consequence of alternative splicing. This review summarizes the differences between the isoforms in terms of the effects on domain structure and hence possible function. The close identity between LTBPs and members of the fibrillin family, mutations in which have been linked directly to Marfan's syndrome, suggests that anomalous expression of LTBPs may be associated with disease. Recent data indicating that differential expression of LTBP1 isoforms occurs during the development of coronary heart disease is considered, together with evidence that modulation of LTBP function, and hence of TGFbeta activity, is associated with a variety of cancers. (+info)Latent TGF-beta Binding Proteins (LTBPs) are a family of extracellular matrix proteins that covalently bind to and facilitate the secretion, transport, and activation of latent TGF-beta (Transforming Growth Factor-beta) complexes.
Latent Transforming Growth Factor-beta (TGF-β) binding proteins (LTBPs) are a family of extracellular matrix proteins that play a crucial role in the regulation and localization of TGF-β, a cytokine involved in various cellular processes such as cell growth, differentiation, and apoptosis. LTBPs bind to and help to stabilize the latent form of TGF-β, which is an inactive form of the cytokine. This binding keeps TGF-β in its inactive state until it is needed for use.
There are four members in the LTBP family (LTBP-1, -2, -3, and -4) that share structural similarities with fibrillin, a major component of microfibrils in the extracellular matrix. LTBPs can undergo proteolytic processing, releasing the latent TGF-β complex from the extracellular matrix, allowing for its activation and subsequent interaction with its receptors on the cell surface.
Abnormalities in LTBP function or expression have been implicated in various diseases, including fibrosis, cancer, and Marfan syndrome. Therefore, understanding the role of LTBPs in TGF-β regulation is essential for developing therapeutic strategies to target these conditions.
Transforming Growth Factor-beta (TGF-β) is a multifunctional cytokine that regulates various cellular processes, including proliferation, differentiation, apoptosis, and extracellular matrix production, through Smad-dependent and Smad-independent signaling pathways.
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.
Beta karyopherins, also known as importin-βs, are a family of transport receptor proteins that facilitate the nuclear import or export of cargo proteins by recognizing specific nuclear localization or nuclear export signals, and interacting with the nuclear pore complex to mediate translocation across the nuclear membrane.
Beta karyopherins, also known as importin-βs or transportins, are a family of nuclear transport receptors that play a crucial role in the shuttling of proteins and RNAs between the cytoplasm and the nucleus. They recognize specific signals on their cargo, such as nuclear localization sequences (NLS) or nuclear export sequences (NES), and mediate their translocation through the nuclear pore complex (NPC).
Beta karyopherins function by binding to their cargo in the cytoplasm, forming a complex that is then recognized by the NPC. Once inside the nucleus, beta karyopherins release their cargo and return to the cytoplasm, where they can bind to new cargoes.
There are several members of the beta karyopherin family, each with distinct specificities for different types of cargoes. Some examples include importin-β1, which is involved in the transport of classical NLS-containing proteins; importin-α, which acts as an adaptor between importin-β1 and its cargo; and transportin-1, which transports RNA-binding proteins.
Dysregulation of beta karyopherin function has been implicated in various diseases, including cancer, neurodegenerative disorders, and viral infections.
Protein binding refers to the interaction between a drug and a protein in the body, where the drug is bound to the protein, altering its pharmacological effect, distribution, metabolism, and excretion.
Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.
In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.
Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.
'Molecular sequence data' refers to the specific arrangement of molecules, such as nucleotides in DNA or amino acids in proteins, that are represented in a linear fashion and used to identify, compare, and analyze biological characteristics or relationships among organisms at the molecular level.
Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.
'Carrier proteins' are membrane-bound transport proteins that facilitate the passage of specific molecules across biological membranes by undergoing conformational changes, thus maintaining cellular homeostasis without altering the gradient.
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.
In Biochemistry and Pharmacology, 'binding sites' refer to specific regions on a macromolecule (such as a protein or nucleic acid) where another molecule (like a drug, ligand, or cofactor) can attach or bind, often influencing the function, activity, or conformation of the macromolecule.
In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.
The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.
In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.
"An amino acid sequence is the specific linear arrangement of amino acids along a polypeptide chain, determined by the genetic code of an organism, that contributes to the unique three-dimensional structure and functional properties of proteins."
An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.
A cell line is a homogeneous population of cells, all originating from a single cell, which has the ability to grow and divide indefinitely under specific culturing conditions, often used in scientific research for consistency and reproducibility.
A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.
Latent TGF-beta binding protein
Rifkin DB (March 2005). "Latent transforming growth factor-beta (TGF-beta) binding proteins: orchestrators of TGF-beta ... The latent TGF-beta binding proteins (LTBP) are a family of carrier proteins. LTBP is a family of secreted multidomain proteins ... Latent+TGF-beta+Binding+Proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH) PDBe-KB provides an ... Todorovic V, Jurukovski V, Chen Y, Fontana L, Dabovic B, Rifkin DB (January 2005). "Latent TGF-beta binding proteins". Int. J. ...
LTBP3
Chen Y, Dabovic B, Annes JP, Rifkin DB (2002). "Latent TGF-beta binding protein-3 (LTBP-3) requires binding to TGF-beta for ... 2003). "Secretion of human latent TGF-beta-binding protein-3 (LTBP-3) is dependent on co-expression of TGF-beta". J. Cell Sci. ... "Latent transforming growth factor-beta binding proteins (LTBPs)--structural extracellular matrix proteins for targeting TGF- ... Koli K, Hyytiäinen M, Ryynänen MJ, Keski-Oja J (2005). "Sequential deposition of latent TGF-beta binding proteins (LTBPs) ...
LTBP1 (gene)
... of TGF-betas is regulated by their association with latency-associated proteins and with latent TGF-beta binding proteins. The ... "TGF-beta 1 binding protein: a component of the large latent complex of TGF-beta 1 with multiple repeat sequences". Cell. 61 (6 ... The protein encoded by this gene belongs to the family of latent TGF-beta binding proteins (LTBPs). The secretion and ... "Latent transforming growth factor-beta binding proteins (LTBPs)--structural extracellular matrix proteins for targeting TGF- ...
TGF beta 1
Saharinen J, Keski-Oja J (August 2000). "Specific sequence motif of 8-Cys repeats of TGF-beta binding proteins, LTBPs, creates ... a hydrophobic interaction surface for binding of small latent TGF-beta". Mol. Biol. Cell. 11 (8): 2691-704. doi:10.1091/mbc. ... TGF beta 1 has been shown to interact with: Decorin, EIF3I LTBP1, TGF beta receptor 1, and YWHAE. GRCh38: Ensembl release 89: ... Many cells synthesize TGF-β and almost all of them have specific receptors for this peptide. TGF-β1, TGF-β2, and TGF-β3 all ...
Integrin beta 6
"Integrin alphaVbeta6-mediated activation of latent TGF-beta requires the latent TGF-beta binding protein-1". The Journal of ... February 1999). "The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary ... February 1999). "The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary ... The principal function of αvβ6 is the activation of cytokine transforming growth factor-b1 (TGF-β1). Latent-TGF-β1 is bound to ...
LTBP2
The protein encoded by this gene belongs to the family of latent transforming growth factor (TGF)-beta binding proteins (LTBP ... "Latent transforming growth factor-beta binding proteins (LTBPs)--structural extracellular matrix proteins for targeting TGF- ... 1995). "Mapping of human and murine genes for latent TGF-beta binding protein-2 (LTBP2)" (PDF). Mamm. Genome. 6 (1): 42-5. doi: ... Latent-transforming growth factor beta-binding protein 2 is a protein that in humans is encoded by the LTBP2 gene. ...
Fibrillin-1
7 eight-cysteine domains homologous with latent TGF-beta binding protein, and a proline-rich region. The FBN-1 gene is involved ... Handford PA (December 2000). "Fibrillin-1, a calcium binding protein of extracellular matrix". Biochimica et Biophysica Acta ( ... Mutations altering the protein can result in a variety of phenotypic effects differing widely in their severity, including ... Fibrillin-1 is a protein that in humans is encoded by the FBN1 gene, located on chromosome 15. It is a large, extracellular ...
TGF beta Activation
"Latent transforming growth factor-beta 1 associates to fibroblast extracellular matrix via latent TGF-beta binding protein". J ... "Latent transforming growth factor-beta binding proteins (LTBPs) structural extracellular matrix proteins for targeting TGF-beta ... This complex remains in the cell until it is bound by another protein called Latent TGF-β-Binding Protein (LTBP), forming a ... Rifkin, D. B. (2005). "Latent transforming growth factor-β (TGF-β) binding proteins: orchestrators of TGF-β availability". J. ...
Transforming growth factor beta
Rifkin DB (March 2005). "Latent transforming growth factor-beta (TGF-beta) binding proteins: orchestrators of TGF-beta ... The primary 3 mammalian types are: TGF beta 1 - TGFB1 TGF beta 2 - TGFB2 TGF beta 3 - TGFB3 A fourth member, TGF beta 4, has ... "Latent transforming growth factor-beta 1 associates to fibroblast extracellular matrix via latent TGF-beta binding protein". ... in a latent form in which it is complexed with two other polypeptides, latent TGF-beta binding protein (LTBP) and latency- ...
Marfan syndrome
Transforming growth factor beta (TGF-β) plays an important role in MFS. Fibrillin-1 directly binds a latent form of TGF-β, ... a receptor protein of TGF-β. Marfan syndrome has often been confused with Loeys-Dietz syndrome, because of the considerable ... The importance of the TGF-β pathway was confirmed with the discovery of the similar Loeys-Dietz syndrome involving the TGFβR2 ... Beta blockers are used to reduce the stress exerted on the aorta and to decrease aortic dilation. If the dilation of the aorta ...
Proteases in angiogenesis
For example, plasminogen activators drive the activation of latent transforming growth factor beta (TGF-β) from bone ECM and ... "Structure-function analysis of the ADAM family of diintegrin-like and metalloproteinase-containing proteins". J. Protein Chem. ... Upon binding of their ligands, Notch-1 and Tie-1 undergo proteolytic cleavage of the ectodomains by ADAM17 and ADAM10. This ... "Plasminogen dependent activation of latent transforming growth factor beta by growing cultures of osteoblast like cells". J. ...
Amphiregulin
TGF-β)-induced fibrosis too, as it has been found to activate latent TGF-β through the activation of integrin-αV complex. In ... It is ligand for epidermal growth factor (EGF) and it is related to transforming growth factor alpha (TGF-alpha). This protein ... The function of amphiregulin in airway fibrosis is related to eosinophils that express EGFR, in which amphiregulin binds to, ... Moreover, macrophage-derived amphiregulin is involved in the transforming growth factor beta ( ...
Alveolar macrophage
The latent complex is covalently linked to the extracellular matrix by binding to latent TGF-β-binding proteins. TGF-β is ... "The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and ... αvβ6 integrin is able to mediate activation of TGF-β by binding to TGF-β1 LAP, which serves as a ligand binding site for the ... Integrins are dimeric cell-surface receptors composed of alpha and beta subunits, which activates TGF-β.< TGF-β is a ...
MMP2
... along with MMP-9 in cleaving latent TGF-β, which has complex interactions with cancer cells. TGF-β generally plays a role in ... More generally, by degrading the ECM, MMPs release growth factors that were previously bound to the ECM, allowing them to bind ... Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix (ECM) in normal ... Montgomery AM, Reisfeld RA, Cheresh DA (September 1994). "Integrin alpha v beta 3 rescues melanoma cells from apoptosis in ...
EGF-like domain
Latent-transforming growth factor beta-binding protein 1). In addition to the aforementioned three disulfide hEGF- and cEGF- ... cEGF-like domains seem to play an unspecific role in this activation by promoting the cleavage of LTBP-1 from TGF-β by various ... Most occurrences of the EGF-like domain are found in the extracellular domain of membrane-bound proteins or in proteins known ... Examples include the coagulation factors VII, IX and X, protein C and its cofactor protein S. Calcium-binding EGF-like domains ...
Elastic fiber
Robertson IB, Horiguchi M, Zilberberg L, Dabovic B, Hadjiolova K, Rifkin DB (September 2015). "Latent TGF-β-binding proteins". ... April 2009). "Dual functions for LTBP in lung development: LTBP-4 independently modulates elastogenesis and TGF-beta activity ... latent transforming growth factor β binding protein 4, and microfibril associated protein 4. In this process tropoelastin, the ... January 2016). "Characterization of Microfibrillar-associated Protein 4 (MFAP4) as a Tropoelastin- and Fibrillin-binding ...
Protein c-Fos
Zhang Y, Feng XH, Derynck R (August 1998). "Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced ... c-Fos is a 380 amino acid protein with a basic leucine zipper region for dimerisation and DNA-binding and a transactivation ... Yang X, Chen Y, Gabuzda D (September 1999). "ERK MAP kinase links cytokine signals to activation of latent HIV-1 infection by ... This includes the cAMP response element binding protein (CREB), the phosphorylation of which induces its association with the ...
Myostatin
... is produced as promyostatin, a precursor protein kept inactive by the latent TGF-β binding protein 3 (LTBP3). ... Myostatin is a secreted growth differentiation factor that is a member of the TGF beta protein family. Myostatin is assembled ... McPherron AC, Lawler AM, Lee SJ (May 1997). "Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member". ... This process includes mitogen-activated protein kinases and binding of the MEF2 transcription factor within the promoter region ...
MiR-155
"Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein beta are targeted by miR-155 in B ... Rai D, Kim SW, McKeller MR, Dahia PL, Aguiar RC (Feb 2010). "Targeting of SMAD5 links microRNA-155 to the TGF-beta pathway and ... Gatto G, Rossi A, Rossi D, Kroening S, Bonatti S, Mallardo M (Nov 2008). "Epstein-Barr virus latent membrane protein 1 trans- ... "Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein beta are targeted by miR-155 in B ...
Macrophage
Both complement proteins and antibodies can bind to antigens and opsonize them. Macrophages have complement receptor 1 (CR1) ... TGF-beta and low levels of IL-12. Tumor-associated macrophages are mainly of the M2 phenotype, and seem to actively promote ... can remain latent in a macrophage via inhibition of phagosome-lysosome fusion; causes brucellosis (undulant fever).[citation ... and 3 (CR3) that recognize pathogen-bound complement proteins C3b and iC3b, respectively, as well as fragment crystallizable γ ...
GDF11
... can bind type I TGF-beta superfamily receptors ACVR1B (ALK4), TGFBR1 (ALK5) and ACVR1C (ALK7), but predominantly uses ... Ge G, Hopkins DR, Ho WB, Greenspan DS (July 2005). "GDF11 forms a bone morphogenetic protein 1-activated latent complex that ... Developmental genes and proteins, TGFβ domain, Aging-related proteins). ... As the key member of the TGF-Beta superfamily, GDF11 represents a promising therapeutic agent for the treatment of a number of ...
NEDD4L
"Latent membrane protein 2A of Epstein-Barr virus binds WW domain E3 protein-ubiquitin ligases that ubiquitinate B-cell tyrosine ... "Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling". Mol. Cell. 36 (3): 457-68. doi:10.1016/j.molcel ... The NEDD4-2 protein consists of an amino-terminal Ca2+-phospholipid binding domain (C2), 4 WW domains (protein-protein ... The WW domains in the protein are responsible for binding the substrates, regulatory proteins and adaptors. These domains ...
Transcription factor Jun
It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the JUN gene. c-jun was ... Zhang Y, Feng XH, Derynck R (August 1998). "Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced ... Yang X, Chen Y, Gabuzda D (September 1999). "ERK MAP kinase links cytokine signals to activation of latent HIV-1 infection by ... Kara CJ, Liou HC, Ivashkiv LB, Glimcher LH (April 1990). "A cDNA for a human cyclic AMP response element-binding protein which ...
IGFBP3
"Interaction of insulin-like growth factor binding protein-3 with latent transforming growth factor-beta binding protein-1". ... also known as alpha-2-macroglobulin receptor or type V TGFβ receptor and the transmembrane protein TMEM219. Both are believed ... "Transferrin is an insulin-like growth factor-binding protein-3 binding protein". The Journal of Clinical Endocrinology and ... "Plasminogen binds the heparin-binding domain of insulin-like growth factor-binding protein-3". The American Journal of ...
CDKN1B
... and latent TGFβ binding protein (LTBP)-4 expression in late stage canine mammary tumours". Veterinary Journal. 186 (3): 379-84 ... Decreased TGF-beta signalling has been suggested to cause loss of p27 expression in this tumor type. A structured cis- ... Translation is regulated by polypyrimidine tract-binding protein(PTB), ELAVL1, ELAVL4, and microRNAs. PTB acts by binding ... inhibitor proteins. The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and ...
Mouse models of breast cancer metastasis
The role of autocrine transforming growth factor beta 1(TGF-β1) signaling on motility and survival in PymT cells derived from ... "Biological activity of cloned mammary tumor virus DNA fragments that bind purified glucocorticoid receptor protein in vitro". ... "From latent disseminated cells to overt metastasis: Genetic analysis of systemic breast cancer progression". Proceedings of the ... Expression of TGFβ in the breast cancer cells of MMTV-ErbB2; MMTV-TGFβ double-transgenic mice can induce higher levels of ...
SMAD (protein)
However, when TGF-B signal is present, this complex localizes to the nucleus, where it associates with Smad4 and binds to the ... The components of the TGF-beta pathway and in particular, the R-Smads, Co-Smad and I-Smads, are represented in the genome of ... Huang XR, Chung AC, Wang XJ, Lai KN, Lan HY (July 2008). "Mice overexpressing latent TGF-beta1 are protected against renal ... Therefore, downregulating ID proteins is a pathway by which TGF-B signaling could arrest the cell cycle. In a DNA microarray ...
2019 in science
Scientists at the University of California, San Diego describe how a protein named Dsup (Damage suppression protein) binds to ... Researchers at University of Nebraska Medical Center describe the role of TGF-beta type II signaling receptor (TGFBR2) in ... 15 March - NASA reports that latent viruses in humans may be activated during space missions, adding possibly more risk to ... a genetic mutation affecting the ATP7B copper-binding protein. Engineers at Duke University report the use of machine learning ...
SNED1
... the latent-TGFβ binding protein 2 (LTBP2), and the basement membrane glycoproteins nidogens 1 and 2. Independently, the STRING- ... The beta sheets are annotated as purple text in the conceptual translation and the alpha-helices are annotated as red text. The ... protein binding, cell-adhesion, and ECM proteins. Splice variants a, b, and e, ihave >99% structural similarity to the protein ... proteins, the jagged proteins, eyes shut homolog proteins, the crumbs homolog proteins, delta and notch-like epidermal growth ...
Regulatory T cell
Vitamin A and TGF-beta promote T cell differentiation into regulatory T cells opposed to Th17 cells, even in the presence of IL ... April 2018). "TGF-β mimic proteins form an extended gene family in the murine parasite Heligmosomoides polygyrus". ... Binding of IL-1β to IL1R2 on the surface of Treg cells does not cause any signal transduction because there is no present ... CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute ...
