A5000395108- NF-κB Signaling Pathways
- Cytokine Signaling Pathways and Interactions
- HER2/EGFR in Cancer Research
- Immune Response and Inflammation
- interferon and immune responses
- Melanoma and MAPK Pathways
- Microbial Natural Products and Biosynthesis
- Natural product bioactivities and synthesis
- Immunotherapy and Immune Responses
- Chemokine receptors and signaling
- Immune Cell Function and Interaction
- Cell death mechanisms and regulation
- Monoclonal and Polyclonal Antibodies Research
- PI3K/AKT/mTOR signaling in cancer
- Lung Cancer Treatments and Mutations
- Cell Adhesion Molecules Research
- Pharmacological Effects of Natural Compounds
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Synthetic Organic Chemistry Methods
- Marine Sponges and Natural Products
- Peptidase Inhibition and Analysis
- Axon Guidance and Neuronal Signaling
- Bone Metabolism and Diseases
- Protein Tyrosine Phosphatases
University of Toyama
2016-2025
Kansai Medical University
2025
University Medical Center
2025
Fujita Health University
2024
Fujita Health University Hospital
2023
Gakushūin School Corporation
2022-2023
Tohoku University
2011-2013
Komatsu (Japan)
2011-2013
Tokyo Institute of Technology
2011-2013
Toyama Prefectural University
2007-2012
Recent investigations have elucidated the cytokine-induced NF-κB activation pathway. IκB kinase (IKK) phosphorylates inhibitors of (IκBs). The phosphorylation targets them for rapid degradation through a ubiquitin-proteasome pathway, allowing nuclear translocation NF-κB. We examined possibility that IKK can phosphorylate p65 subunit as well in activation. In cytoplasm HeLa cells, was rapidly phosphorylated response to TNF-α time dependent manner similar phosphorylation. vitro with GST-fused...
Phosphatidylinositol 3′-kinase (PI3K) and the serine/threonine kinase AKT have critical roles in phosphorylating transactivating p65 subunit of nuclear factor κB (NF-κB) response to pro-inflammatory cytokines interleukin-1 (IL-1) tumor necrosis (TNF). Mouse embryo fibroblasts (MEFs) lacking either α or β IκB (IKK) were deficient NF-κB-dependent transcription following treatment with IL-1 TNF. However, contrast IKKβ-null MEFs, IKKα-null MEFs not substantially defective cytokine-stimulated...
The activation of NF-κB has been shown to be regulated by multiple phosphorylations IκBs and the p65 subunit. Here, we characterized intracellular signaling pathway leading phosphorylation on Ser-536 using a novel anti-phospho-p65 (Ser-536) antibody. endogenous was rapidly phosphorylated in response wide variety stimulants including TNF-α cytoplasm dephosphorylated nucleus. TNF-α-but not IL-1β-induced severely impaired murine embryonic fibroblasts derived from traf2-/-traf5-/- mice. Bay...
AbstractThe receptor activator of NF-κB (RANK) and its ligand RANKL are key molecules for differentiation activation osteoclasts. stimulates transcription factors AP-1 through mitogen-activated protein kinase (MAPK) activation, IκB (IKK) activation. Tumor necrosis factor receptor-associated 6 (TRAF6) is essential these kinases. In the interleukin-1 signaling pathway, TAK1 MAPK (MAPKKK) mediates IKK via interaction with TRAF6, TAB2 acts as an adapter linking TRAF6. Here, we demonstrate that...
Several mitogen-activated protein kinase kinases play critical roles in nuclear factor-κB (NF-κB) activation. We recently reported that the overexpression of transforming growth factor-β-activated 1 (TAK1), a member family, together with its activator TAK1-binding (TAB1) stimulates NF-κB Here we investigated molecular mechanism TAK1-induced Dominant negative mutants IκB (IKK) α and IKKβ inhibited TAK1 activated IKKα presence TAB1. were coimmunoprecipitated absence TAB1-induced activation...
Abstract Peritoneal carcinomatosis is a frequent cause of death in patients with advanced gastric carcinoma. Because chemokines are now considered to play an important role the metastasis various malignancies, we hypothesized that they may be involved development peritoneal by Human carcinoma cell lines, which were all highly efficient generating malignant ascites nude mice upon i.p. inoculation, selectively expressed CXCR4 mRNA and protein. In particular, NUGC4 cells at high levels showed...
Transforming growth factor-beta-activated kinase 1 (TAK1) mitogen-activated protein has been shown to be activated by cellular stresses including tumor necrosis factor-alpha (TNF-alpha). Here, we characterized the molecular mechanisms of stress-induced TAK1 activation, focusing mainly on phosphorylation at Thr-187 and Ser-192 in activation loop. are conserved among species from Caenorhabditis elegans human, their replacement with Ala resulted inactivation TAK1. Immunoblotting a novel...
CXCL16 is a new member of the chemokine superfamily, which exists in transmembrane as well soluble form. Its receptor CXCR6 detected on CD4(+) T cells, CD8(+) and natural killer cells. Here, we report significant correlation expression by tumor cells with infiltration prognosis colorectal cancer (CRC). We first found that was consistently up-regulated more tissues than normal mucosa derived from same CRC patients. Four human cell lines also expressed mRNA secreted CXCL16. next examined...
The recruitment of osteoclast precursors toward osteoblasts and subsequent cell-cell interactions are critical for differentiation. Chemokines known to regulate cell migration adhesion. CX3CL1 (also called fractalkine) is a unique membrane-bound chemokine that has dual functions cells expressing its receptor CX3CR1: potent chemotactic factor in soluble form type efficient adhesion molecule form. In this paper, we demonstrate novel role osteoblast-induced We found selectively expressed...
Abstract Crosstalk between inflammatory signalling pathways and receptor tyrosine kinases has been revealed as an indicator of cancer malignant progression. In the present study, we focus on EphA2 kinase, which is overexpressed in many human cancers. It reported that ligand-independent phosphorylation at Ser-897 induced by Akt. We show cytokines promote RSK-, not Akt-, dependent Ser-897. addition, RSK–EphA2 pathway controls cell migration invasion metastatic breast cells. Moreover,...
TAK1 is a mitogen-activated protein kinase (MAP3K) that involved in the c-Jun N-terminal kinase/p38 MAPKs and NF-kappaB signaling pathways. Here, we characterized molecular mechanisms of activation by its specific activator TAB1. Autophosphorylation two threonine residues loop was necessary for activation. Association with induction autophosphorylation required C-terminal 24 amino acids TAB1, but full additional Ser/Thr rich sequences. These results demonstrated association between domain...
The IkappaB kinase (IKK)-related NAK (also known as TBK or T2K) contributes to the activation of NF-kappaB-dependent gene expression. Here we identify NAP1 (for NAK-associated protein 1), a that interacts with and its relative IKK epsilon IKKi). activates facilitates oligomerization. Interestingly, NAK-NAP1 complex itself effectively phosphorylated serine 536 p65/RelA subunit NF-kappaB, this activity was stimulated by tumor necrosis factor alpha (TNF-alpha). Overexpression specifically...
The B cell antigen receptor (BCR)–mediated activation of IκB kinase (IKK) and nuclear factor–κB require protein C (PKC)β; however, the mechanism by which PKCβ regulates IKK is unclear. Here, we demonstrate that another kinase, TGFβ-activated (TAK)1, essential for in response to BCR stimulation. TAK1 interacts with phosphorylated CARMA1 (also known as caspase recruitment domain [CARD]11, Bimp3) this interaction mediated PKCβ. also recruited CARMA1–Bcl10–mucosal-associated lymphoid tissue 1...
Several lines of evidence show the importance angiotensin II (AII) in renal injuries, especially when hemodynamic abnormalities are involved. To elucidate role AII immune-mediated injury, we studied anti-glomerular basement membrane (GBM) nephritis type 1a receptor (AT1a)-deficient homozygous (AT1a-/-) and wild-type (AT1a+/+) mice. A transient activation renin-angiotensin system (RAS) was observed both groups mice at around day 1. expression monocyte chemoattractant protein-1 (MCP-1)...
Receptor-interacting protein (RIP) plays a critical role in tumor necrosis factor-alpha (TNF-alpha)-induced IkappaB kinase (IKK) activation and subsequent of transcription factor NF-kappaB. However, the molecular mechanism by which RIP mediates TNF-alpha-induced NF-kappaB is not completely defined. In this study, we have found that TAK1 recruited to TNF-alpha receptor complex RIP-dependent manner following stimulation 1 (TNF-R1). Moreover, forced recruitment TNF-R1 absence sufficient mediate...
The cytokine interleukin-1 (IL-1) mediates immune and inflammatory responses by activating the transcription factor nuclear kappaB (NF-kappaB). Although transforming growth factor-beta-activated kinase 1 (TAK1) mitogen-activated protein (MAPK) 3 (MEKK3) are both crucial for IL-1-dependent activation of NF-kappaB, their potential functional physical interactions remain unclear. Here, we showed that TAK1-mediated NF-kappaB required transient formation a signaling complex included tumor...
Human T lymphocyte virus type I (HTLV-I) can be transmitted into several inbred strains of newborn and adult rats by inoculating newly established HTLV-I-immortalized rat cell lines or the human line MT-2. The transmission efficiency exceeds 80%, regardless strain differences age at transmission. production anti-HTLV-I antibodies significantly differs among depends on time Rats neonatally inoculated with HTLV-I-positive cells generally become seronegative HTLV-I carriers throughout their...
The concomitant addition of the histone deacetylase inhibitor and DNA methyltransferase to culture medium an entomopathogenic fungus, Isaria tenuipes, greatly enhanced its secondary metabolite production led isolation tenuipyrone (1), a novel polyketide with unprecedented tetracyclic ring system bearing spiroketal structural component, along two known C10-polyketides, cephalosporolide B (2), which is plausible biosynthetic precursor 1, F (3).