A5101707619- TGF-β signaling in diseases
- Neonatal Health and Biochemistry
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Methemoglobinemia and Tumor Lysis Syndrome
- Heme Oxygenase-1 and Carbon Monoxide
- Optical Imaging and Spectroscopy Techniques
- Non-Invasive Vital Sign Monitoring
- Neonatal and fetal brain pathology
- Pharmacogenetics and Drug Metabolism
- Metabolism and Genetic Disorders
- Drug Transport and Resistance Mechanisms
- Cancer-related gene regulation
- Angiogenesis and VEGF in Cancer
- Birth, Development, and Health
- Cardiac Imaging and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Neonatal Respiratory Health Research
- Kruppel-like factors research
- Genetic factors in colorectal cancer
- Particle Detector Development and Performance
- Liver Disease Diagnosis and Treatment
- Radiation Detection and Scintillator Technologies
- Neuroscience of respiration and sleep
- Signaling Pathways in Disease
Showa Pharmaceutical University
2015-2024
Kagawa University
2014-2023
Tokyo University of Science
1995-2023
Azabu University
2021
Kaken Pharmaceutical (Japan)
2013-2018
Tokushima University
1988-2016
Target (United States)
2016
National Institutes of Health
2016
University of Tsukuba
2004-2015
Kyushu University
1995-2015
Smad proteins have been identified as mediators of intracellular signal transduction by members the transforming growth factor-β (TGF-β) superfamily, which affect cell proliferation, differentiation, well pattern formation during early vertebrate development. Following receptor activation, Smads are assembled into heteromeric complexes consisting a pathway-restricted and common Smad4 that subsequently translocated nucleus where they thought to play an important role in gene transcription....
Transforming growth factor-beta (TGF-beta) and bone morphogenetic proteins (BMPs) signal via distinct type I II receptors Smad proteins. A nine amino acid sequence between kinase subdomains IV V in receptors, termed the L45 loop, has been shown to be important conferring signalling specificity. We examined responses of a mutant TGF-beta receptor (TbetaR-I) BMPR-IB, which regions these two were exchanged. Swapping four residues that are different BMPR-IB for those TbetaR-I, vice versa,...
Transforming growth factor-β (TGF-β) is a pluripotent cytokine that regulates cell fate and plasticity in normal tissues tumors. The multifunctional cellular responses evoked by TGF-β are mediated the canonical SMAD pathway noncanonical pathways, including mitogen-activated protein kinase (MAPK) pathways phosphatidylinositol 3'-kinase (PI3K)-protein B (AKT) pathway. We found activated PI3K manner dependent on activity of E3 ubiquitin ligase tumor necrosis factor receptor-associated 6...
Bone morphogenetic proteins (BMPs) are multifunctional that regulate the proliferation, differentiation, and migration of a large variety cell types. Like other members transforming growth factor-beta family, BMPs elicit their cellular effects through activating specific combinations type I II serine/threonine kinase receptors downstream effector proteins, which termed Smads. In present study, we investigated BMP receptor/Smad expression signaling in endothelial cells (ECs) examined on EC...
Interferon regulatory factor 1 (IRF-1) and IRF-2 are structurally similar DNA-binding factors which were originally identified as regulators of the type I interferon (IFN) system; former functions a transcriptional activator, latter represses IRF-1 function by competing for same cis elements. More recent studies have revealed new roles two in regulation cell growth; manifest antioncogenic oncogenic activities, respectively. In this study, we determined structures chromosomal locations human...
Transforming growth factor beta (TGF-beta) signals from membrane to nucleus through serine/threonine kinase receptors and their downstream effector molecules, termed Smad proteins. Recently, Smad6 Smad7 were identified, which antagonize TGF-beta family signaling by preventing the activation of signal-transducing complexes. Here we report that Smad7, but not Smad6, inhibits TGF-beta1-induced inhibition expression immediate early response genes, including Smad7. Interestingly, in absence...
CYP3A4 is the adult‐specific form of cytochrome P 450 in human livers [Komori, M., Nishio, K., Kitada, Shiramatsu, Muroya, Soma, Nagashima, K. & Kamataki, T. (1990) Biochemistry 29 , 4430–4433]. The sequences three genomic clones for were analyzed all exons, exon‐intron junctions and 5′‐flanking region from major transcription site to nucleotide position ‐1105, compared with those CYP3A7 gene, a fetal‐specific humans. results showed that identity between genes was 91%, each had...
Transforming growth factor-beta (TGF-beta) elicits cellular effects by activating specific Smad proteins that control the transcription of target genes. Whereas there is growing evidence are TGF-beta type I receptor-initiated intracellular pathways distinct from pivotal pathway, their physiological importance in signaling not well understood. Therefore, we generated receptors (also termed ALK5s) with mutations L45 loop kinase domain, ALK5(D266A) and ALK5(3A). These mutants showed retained...
Abstract Background: Transforming growth factor‐β (TGF‐β) initiates intracellular signalling by inducing the formation of a heteromeric complex between TGF‐β type I (TβR‐I) and II serine/threonine kinase receptors (TβR‐II). After activation TβR‐I TβR‐II kinase, specific receptor‐regulated Smads (R‐Smads) are phosphorylated kinase. Smad anchor for receptor (SARA), which contains FYVE finger domain, regulates subcellular localization R‐Smads presents them to TβR‐I. However, it is unclear where...
Transcription of germ-line immunoglobulin heavy chain genes conditions them to participate in isotype switch recombination. Transforming growth factor-beta1 (TGF-beta1) stimulates promoter elements located upstream the IgA1 and IgA2 regions, designated Ialpha1 Ialpha2, contributes development IgA responses. We demonstrate that intracellular Smad proteins mediate activation by TGF-beta. TGF-beta type 1 receptor (ALK-5), activin IB (ALK-4), "orphan" ALK-7 trans-activate promoter, thus raising...
Parallel measurements of the thermodynamics (free-energy, enthalpy, entropy and heat-capacity changes) ligand binding to FK506 protein (FKBP-12) in H2O D2O have been performed an effort probe energetic contributions single protein-ligand hydrogen bonds formed reactions. Changing tyrosine-82 phenylalanine FKBP-12 abolishes bond interactions complexes with tacrolimus or rapamycin leads a large apparent enthalpic stabilization both D2O. High-resolution crystallographic analysis reveals that two...
Vascular development depends on transforming growth factor beta (TGFbeta), but whether signalling of this protein is required for the endothelial cells (ECs), vascular smooth muscle (VSMCs) or both unclear. To address this, we selectively deleted type I (ALK5, TGFBR1) and II (TbetaRII, TGFBR2) receptors in mice. Absence either receptor ECs resulted defects yolk sac, as seen mice lacking all cells, causing embryonic lethality at day (E)10.5. Deletion TbetaRII specifically VSMCs also sac;...