A5047622434- Cell Adhesion Molecules Research
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Platelet Disorders and Treatments
- Hippo pathway signaling and YAP/TAZ
- Cellular Mechanics and Interactions
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- Protein Kinase Regulation and GTPase Signaling
- Chemokine receptors and signaling
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- MicroRNA in disease regulation
- Phagocytosis and Immune Regulation
- Ubiquitin and proteasome pathways
- Glycosylation and Glycoproteins Research
- Retinoids in leukemia and cellular processes
- Cell Image Analysis Techniques
- NF-κB Signaling Pathways
- Cancer Immunotherapy and Biomarkers
- Wnt/β-catenin signaling in development and cancer
- Cancer-related molecular mechanisms research
- Protein Tyrosine Phosphatases
- Eicosanoids and Hypertension Pharmacology
- Quinazolinone synthesis and applications
Kitasato University
2012-2023
Tokai University
2023
Tokyo University of the Arts
2023
The University of Tokyo
2000-2023
Tokyo University of Science
2000-2020
Japan Science and Technology Agency
2014
Kwansei Gakuin University
2010-2011
Kansai Medical University
2005-2010
Max Planck Institute of Neurobiology
2010
Medizinische Hochschule Hannover
2010
Chemokines arrest circulating lymphocytes within the vasculature through rapid up-regulation of leukocyte integrin adhesive activity, promoting subsequent lymphocyte transmigration. However, key regulatory molecules regulating this process have remained elusive. Here, we demonstrate that Rap1 plays a pivotal role in chemokine-induced activation and migration. was activated by secondary lymphoid tissue chemokine (SLC; CCL21) stromal-derived factor 1 (CXCL4) treatment seconds. Inhibition Spa1,...
To identify the intracellular signals which increase adhesiveness of leukocyte function-associated antigen 1 (LFA-1), we established an assay system for activation-dependent adhesion through LFA-1/intercellular molecule ICAM-1 using mouse lymphoid cells reconstituted with human LFA-1 and then introduced constitutively active forms signaling molecules. We found that phorbol myristate acetate (PMA)-responsive protein kinase C (PKC) isotypes (alpha, betaI, betaII, delta) or...
Abstract Mesenchymal stromal cells are crucial components of secondary lymphoid organs (SLOs). Organogenesis SLOs involves specialized cells, designated tissue organizer (LTo) in the embryonic anlagen; adult, several distinct lineages construct elaborate architecture and regulate lymphocyte compartmentalization. The relationship between LTo adult however, remains unclear, as does precise number cell types that constitute mature unclear. From mouse lymph nodes, we established a...
Activation of T cells by antigen requires adhesive interactions with antigen-presenting (APC) in which leukocyte function-associated 1 (LFA-1) and intercellular adhesion molecules (ICAMs) are important. However, it is not well understood what signaling regulate this process how the modulation events influences T-cell activation. Here we show that Rap1 activated an antigen-dependent manner accumulated at contact site antigen-loaded APC. Inhibition activation a dominant-negative or SPA-1,...
Human T-cell leukemia virus type 1 (HTLV-1) causes both a neoplastic disease and inflammatory diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 basic leucine zipper factor (HBZ) gene is encoded in the minus strand of proviral DNA constitutively expressed infected cells ATL cells. HBZ increases number regulatory T (Treg) by inducing Foxp3 transcription. Recent studies have revealed that some CD4⁺Foxp3⁺ are not terminally differentiated but...
Chemokines promote the delivery and proper organization of an integrin at leading edge migrating lymphocytes.
The small GTPase, Rap1, is a potent activator of leukocyte integrins and enhances the adhesive activity lymphocyte function-associated antigen-1 (LFA-1) when stimulated by T cell receptor (TCR) or chemokines. However, mechanism which Rap1 activated remains unclear. Here, we demonstrate that phospholipase C (PLC)-γ1 plays critical role in signaling pathway leading to activation triggered TCR. In Jurkat cells, TCR cross-linking persistent activation, SDF-1 (CXCL12) transiently. A inhibitor,...
Rap1 is a potent inside-out signal that increases LFA-1 adhesive activity. In this study, we have defined the cytoplasmic region of alphaL and beta2 integrin are required for Rap1-stimulated adhesion subsequent migration on ICAM-1. Human bearing truncated point-mutated regions were reconstituted in mouse IL-3-dependent proB cells, BAF/3. Truncation alphaL, but not subunit region, abolished Rap1V12-dependent to The alanine substitution two lysine residues (K1097/K1099) was found be critical...
Targeted positioning of water channel aquaporin‐2 (AQP2) strictly regulates body homeostasis. Trafficking AQP2 to the apical membrane is critical reabsorption in renal collecting ducts. Controlled suggests existence proteins that interact with AQP2. A biochemical search for AQP2‐interacting led identification PDZ‐domain containing protein, signal‐induced proliferation‐associated gene‐1 (SPA‐1) which a GTPase‐activating protein (GAP) Rap1. The distribution SPA‐1 coincided site colocalization...
It has been reported that src family protein-tyrosine kinases were expressed specifically in a certain lineage or differentiation stage of hematopoietic cells. To understand the molecular basis for and function monocyte/macrophage, we investigated expressions genes by HL-60 cells stimulated with differentiation-inducing agents. TPA vitamin D3 (D3) used as stimulants monocytic development, since each agent known to induce phenotypically specific The fyn, fgr, lyn characteristically...
The Rap1 small GTPase has been implicated in regulation of integrin-mediated leukocyte adhesion downstream various chemokines and cytokines many aspects inflammatory immune responses. However, the mechanism for signaling remains unclear. RA-GEF-2 is a member multiple-member family guanine nucleotide exchange factors (GEFs) characterized by possession Ras/Rap1-associating domain, interacting with M-Ras-GTP as an effector, addition to GEF catalytic domain. Here, we show that specifically...
The Ecotropic viral integration site 1 (Evi1) is a zinc finger transcription factor, which located on chromosome 3q26, over-expression in some acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Elevated Evi1 expression AML associated with unfavorable prognosis. Therefore, one of the strong candidate molecular target therapy for leukemia. MicroRNAs (miRNAs) are small non-coding RNAs, vital to many cell functions that negatively regulate gene by translation or inducing...
CD98 is a multifunctional heterodimeric membrane protein involved in the regulation of cell adhesion as well amino acid transport. We show that cross‐linking persistently activates Rap1 GTPase LFA‐1‐dependent manner and induces LFA‐1/ICAM‐1‐mediated lymphocytes. Specific phosphatidylinositol‐3‐kinase (PI3K) inhibitors suppressed both LFA‐1 activation Rap1GTP generation, abrogation by retroviral over‐expression specific activating protein, SPA‐1, totally inhibited adhesion. These results...
Integrin α<sub>5</sub>β<sub>1</sub>, a major fibronectin receptor, functions in wide variety of biological phenomena. We have found that α2–8-linked oligosialic acids with 5 ≤ degree polymerization (DP) 7 occur on integrin α<sub>5</sub> subunit the human melanoma cell line G361. The immunoprecipitated anti-integrin antibody reacted monoclonal 12E3, which recognizes oligo/polysialic acid DP ≥ but not polyclonal H.46 recognizing 8. occurrence was further demonstrated by fluorometric...
To investigate the possible roles of Ras/Rho family members in inside-out signals to activate integrins, we examined ability small GTPases stimulate avidity α<sub>5</sub>β<sub>1</sub> (VLA-5) fibronectin bone marrow-derived mast cells. We found that both Ha-Ras<sup>Val-12</sup> and R-Ras<sup>Val-38</sup> had strong stimulatory effects on adhesion ligand binding activity VLA-5 fibronectin. However, only Ha-Ras<sup>Val-12</sup>-, but not R-Ras<sup>Val-38</sup>-induced was inhibited by...