A5015307451- NF-κB Signaling Pathways
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- interferon and immune responses
- Geological and Geochemical Analysis
- Immune Cell Function and Interaction
- Electrochemical sensors and biosensors
- Geology and Paleoclimatology Research
- earthquake and tectonic studies
- Analytical Chemistry and Sensors
- Atmospheric and Environmental Gas Dynamics
- Cytokine Signaling Pathways and Interactions
- Advanced Biosensing Techniques and Applications
- Molecular Junctions and Nanostructures
- Protein Kinase Regulation and GTPase Signaling
- Cell death mechanisms and regulation
- Conducting polymers and applications
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- Geological and Geophysical Studies
- Methane Hydrates and Related Phenomena
- Fullerene Chemistry and Applications
- Advanced biosensing and bioanalysis techniques
- Electrochemical Analysis and Applications
- Boron and Carbon Nanomaterials Research
Sanyo-Onoda City University
2019-2023
RIKEN Center for Integrative Medical Sciences
2008-2022
Tsuchiura Kyodo General Hospital
2021
University of Toyama
2007-2012
Nagoya University
1997-2009
Tokyo Medical and Dental University
2000-2005
Tokyo Institute of Technology
1986-2005
Okayama University
1997
B cell receptor (BCR) recognition of membrane-bound antigen initiates a spreading and contraction response, the extent which is controlled through formation signaling-active BCR-antigen microclusters ultimately affects outcome activation. We followed genetic approach to define molecular requirements BCR-induced microcluster formation. identify key role for phospholipase C-γ2 (PLCγ2), Vav, linker, Bruton's tyrosine kinase in highly coordinated “microsignalosomes,” efficient assembly...
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...
Protein kinase C (PKC) beta has been reported (Shinohara, H., T. Yasuda, Y. Aiba, H. Sanjo, M. Hamadate, Watarai, Sakurai, and Kurosaki. 2005. J. Exp. Med. 202:1423-1431; Sommer, K., B. Guo, J.L. Pomerantz, A.D. Bandaranayake, M.E. Moreno-Garcia, Y.L. Ovechkina, D.J. Rawlings. Immunity. 23:561-574) to play a crucial role in B cell receptor (BCR)-mediated IkappaB (IKK) activation through phosphorylation of caspase recruitment domain 11, Bimp3 (CARMA1). However, it remains unclear whether this...
A switchlike response in nuclear factor-κB (NF-κB) activity implies the existence of a threshold NF-κB signaling module. We show that CARD-containing MAGUK protein 1 (CARMA1, also called CARD11)-TAK1 (MAP3K7)-inhibitor (IκB) kinase-β (IKKβ) module is switch mechanism for activation B cell receptor (BCR) signaling. Experimental and mathematical modeling analyses showed IKK regulated by positive feedback from IKKβ to TAK1, generating steep dose BCR stimulation. Mutation scaffolding CARMA1 at...
Dok-1 and Dok-2 are closely related rasGAP-associated docking proteins expressed preferentially in hematopoietic cells. Although they phosphorylated upon activation of many protein tyrosine kinases (PTKs), including those coupled with cytokine receptors oncogenic PTKs like Bcr-Abl, their physiological roles largely unidentified. Here, we generated mice lacking and/or Dok-2, which included the double-deficient succumbed to myeloproliferative disease resembling human chronic myelogenous...
Endotoxin, a bacterial lipopolysaccharide (LPS), causes fatal septic shock via Toll-like receptor (TLR)4 on effector cells of innate immunity like macrophages, where it activates nuclear factor κB (NF-κB) and mitogen-activated protein (MAP) kinases to induce proinflammatory cytokines such as tumor necrosis (TNF)-α. Dok-1 Dok-2 are adaptor proteins that negatively regulate Ras–Erk signaling downstream tyrosine (PTKs). Here, we demonstrate LPS rapidly induced the phosphorylation function these...
NF-κB is a transcription factor that activates super enhancers (SEs) and typical (TEs) triggers threshold graded gene expression, respectively. However, the mechanisms by which selectively participates in these remain unclear. Here we show using mouse primary B lymphocytes SE activity simultaneously associates with chromatin opening enriched binding, resulting higher fold change expression upon cell receptor (BCR) activation. The results from longer DNA, whereas response explained synergy...
Recently, several papers indicated that the surface plasmon resonance (SPR) technique was available to monitor stimulation responses of mammalian cells adhered on sensor chips. On other hand, newly developed two-dimensional SPR (2D-SPR) imager system can obtain 2D-images local refractive index change a gold thin film. From these backgrounds, we expected 2D-SPR visualize individual response many cells, simultaneously. Here, report observation an allergenic model mast cell, rat basophilic...
Transcription factor nuclear kappa B (NF-κB) shows cooperative switch-like activation followed by prolonged oscillatory translocation in response to extracellular stimuli. These dynamics are important for of the NF-κB transcriptional machinery, however, activity regulated coordinated actions these has not been elucidated at system level. Using a variety cells with artificially rewired signaling networks, we show that oscillations and can be dissected that, under some conditions, two...
The CARMA1/CARD11-BCL10-MALT1 (CBM) complex bridges T and B cell antigen receptor (TCR/BCR) ligation to MALT1 protease activation canonical nuclear factor κB (NF-κB) signaling. Using unbiased mass spectrometry, we discover multiple serine phosphorylation sites in the C terminus after activation. Phospho-specific antibodies reveal that CBM-associated is transiently hyper-phosphorylated upon TCR/CD28 co-stimulation. We identify a dual role for CK1α as kinase essential CBM signalosome assembly...
The transcription factor NF-κB, which plays an important role in cell fate determination, is involved the activation of super-enhancers (SEs). However, biological functions NF-κB SEs gene control are not fully elucidated. We investigated characteristics NF-κB-mediated SE activity using fluorescence imaging RelA, single-cell transcriptome and chromatin accessibility analyses anti-IgM-stimulated B cells. formation stimulation-induced nuclear RelA foci was abolished presence hexanediol,...
B-cell receptor (BCR) signaling plays a critical role in activation and humoral immunity. In this study, we discovered function of leucine-rich repeat kinase 1 (LRRK1) BCR-mediated immune responses. Lrrk1(-/-) mice exhibited altered B1a-cell development basal immunoglobulin production. addition, these failed to produce IgG3 antibody response T cell-independent type 2 antigen due defects class-switch recombination. Concomitantly, B cells lacking LRRK1 profound defect proliferation survival...
The adaptor protein CARMA1 is required for antigen receptor-triggered activation of IKK and JNK in lymphocytes. Once activated, the events that subsequently turn off signalosome are unknown. In this study, we found receptor-activated underwent lysine 48 (K48) polyubiquitination proteasome-dependent degradation. MAGUK region was an essential player event; SH3 GUK domains contained main ubiquitin acceptor sites, deletion a Hook domain (an important structure maintaining inactive proteins)...
The CARMA1-BCL10-MALT1 (CBM) complex bridges T cell receptor (TCR) signaling to the canonical IκB kinase (IKK)/NF-κB pathway. CBM constitutes a cluster of more than 1 Mio Dalton. Little is known about factors that facilitate rapid assembly and maintenance this dynamic higher order complex. Here, we report novel interaction aryl hydrocarbon (AHR) interacting protein (AIP) molecular scaffold CARMA1. In cells, transient binding CARMA1 AIP enhanced formation Thereby, promoted optimal IKK/NF-κB...
Dok‐1 is a common substrate of many protein tyrosine kinases (PTKs). It recruits rasGAP and other SH2‐containing proteins negatively regulates Ras‐Erk signalling downstream PTKs. However, the mechanisms its inhibitory effect are yet unclear. Here, series C‐terminal deletion mutants delineated core domain for inhibition Erk from 334 to 346 amino acid, which contains two SH2‐binding motifs having Tyr‐336 or Tyr‐340. The tyrosine‐to‐phenylalanine (YF) substitution(s) at and/or Tyr‐340 lost...