- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Oral and Maxillofacial Pathology
- Protein Kinase Regulation and GTPase Signaling
- Kruppel-like factors research
- Cellular transport and secretion
- Bone and Dental Protein Studies
- Signaling Pathways in Disease
- Endoplasmic Reticulum Stress and Disease
- Cancer, Hypoxia, and Metabolism
- dental development and anomalies
- Ubiquitin and proteasome pathways
- Metabolism, Diabetes, and Cancer
- RNA Research and Splicing
- Bone Tumor Diagnosis and Treatments
- Pancreatitis Pathology and Treatment
- Cancer-related Molecular Pathways
- Oral Health Pathology and Treatment
- Pancreatic function and diabetes
- Indoor Air Quality and Microbial Exposure
- Genetics and Neurodevelopmental Disorders
- Oral and gingival health research
- Carcinogens and Genotoxicity Assessment
- Head and Neck Cancer Studies
- Liver Disease Diagnosis and Treatment
Kagoshima University
2015-2024
University of Nebraska Medical Center
2017
Kagoshima Prefectural College
2014
Hiroshima University
1996-2006
The University of Tokyo
2002
Hiroshima Institute of Technology
2001
Japan Science and Technology Agency
2000
National Institute of Infectious Diseases
1997
Kobe University
1992-1996
National Institute for Physiological Sciences
1993
The regulators of G protein signaling (RGS) domain Axin, a negative regulator the Wnt pathway, made complex with full-length adenomatous polyposis coli (APC) in COS, 293, and L cells but not truncated APC SW480 or DLD-1 cells. RGS directly interacted region containing 20-amino acid repeats that 15-amino APC, although both regions are known to bind β-catenin. In seven repeats, latter five bound Axin. Axin β-catenin simultaneously APC. Furthermore, stimulated degradation COS Taken together our...
The N-terminal region of Dvl-1 (a mammalian Dishevelled homolog) shares 37% identity with the C-terminal Axin, and this related is named DIX domain. functions domains Axin were investigated. By yeast two-hybrid screening, domain was found to interact Dvl-3, a second relative. Dvl-3 directly bound one another. Furthermore, formed homo-oligomer. also homo-oligomer, its necessary. Dvl-1, including domain, directly. inhibited Axin-promoted glycogen synthase kinase 3β-dependent phosphorylation...
In a previous study (H. Shirataki, K. Kaibuchi, T. Yamaguchi, Wada, H. Horiuchi, and Y. Takai, J. Biol. Chem. 267:10946-10949, 1992), we highly purified from bovine brain crude membranes the putative target protein for smg p25A/rab3A p25, ras p21-related small GTP-binding implicated in neurotransmitter release. this study, have isolated sequenced cDNA of library. The had an open reading frame encoding 704 amino acids with calculated M(r) 77,976. We tentatively refer to as rabphilin-3A....
In a previous study (H. Shirataki, K. Kaibuchi, T. Yamaguchi, Wada, H. Horiuchi, and Y. Takai, J. Biol. Chem. 267:10946-10949, 1992), we highly purified from bovine brain crude membranes the putative target protein for smg p25A/rab3A p25, ras p21-related small GTP-binding implicated in neurotransmitter release. this study, have isolated sequenced cDNA of library. The had an open reading frame encoding 704 amino acids with calculated M(r) 77,976. We tentatively refer to as rabphilin-3A....
Using a yeast two-hybrid method, we identified novel protein which interacts with glycogen synthase kinase 3beta (GSK-3beta). This had 44% amino acid identity Axin, negative regulator of the Wnt signaling pathway. We designated this Axil for Axin like. Like ventralized Xenopus embryos and inhibited Xwnt8-induced axis duplication. was phosphorylated by GSK-3beta. bound not only to GSK-3beta but also beta-catenin, GSK-3beta-binding site distinct from beta-catenin-binding site. Furthermore,...
Wnts are secreted ligands that consist of 19 members in humans, regulate cell proliferation, differentiation, motility and fate many stages including the embryonic stage tumorigenesis. bind to surface receptors named Frizzleds LRPs, transduce their signals through β‐catenin‐dependent ‐independent intracellular pathways. Gliomas one most common intracranial tumors. exhibit a progression associated with widespread infiltration into surrounding neuronal tissues. However, molecular mechanisms...
Wnt5b is a member of the same family proteins as Wnt5a, overexpression which associated with cancer aggressiveness. also suggested to be involved in progression, however, details remain unclarified. We analyzed biochemical properties purified and mode secretion by cells. was glycosylated at three asparagine residues lipidated one serine residue, these post‐translational modifications were essential for secretion. Purified showed Dvl2 phosphorylation Rac activation abilities similar extent...
Ral-binding protein 1 (RalBP1) is a putative effector of Ral and exhibits GTPase activating activity for Rac CDC42. To clarify the function RalBP1, we isolated novel that interacts with RalBP1 by yeast two-hybrid screening designated it POB1 (partner RalBP1). consists 521 amino acids, shares homology Eps15, which has been identified as an epidermal growth factor (EGF) receptor substrate, two proline-rich motifs. The mRNA was expressed in cerebrum, cerebellum, lung, kidney, testis. interacted...
Rabphilin-3A is a putative target molecule for rab3A p25/smg p25A, which member of ras p21-related small GTP-binding protein and implicated in neurotransmitter release from the synapse. has two copies an internal repeat that are homologous to C2 domains kinase C, synaptotagmin, phospholipase A2, known bind phospholipid Ca(2+)-dependent manner. In current study, we have investigated functional or rabphilin-3A by use three recombinant proteins as follows: full (1-704 amino acids), N-terminal...
Dvl is a key protein that transmits the Wnt signal to canonical beta-catenin pathway and noncanonical planar cell polarity (PCP) pathway. We studied roles of Rho-associated kinase (Rho-kinase), which activated by in PCP mammalian cells. The expression Dvl-1, Wnt-1, or Wnt-3a Rho-kinase COS cells, this activation was inhibited Rho-binding domain Rho-kinase. Dvl-1 PC12 cells Rho nerve growth factor (NGF)-induced neurite outgrowth. This inhibition reversed inhibitor but not c-Jun N-terminal...
Adenomatous polyposis coli gene product (APC) functions as a tumor suppressor and its mutations in familial adenomatous colorectal cancers lead to the accumulation of cytoplasmic β-catenin. The molecular mechanism by which APC regulates stability β-catenin was investigated. central region APC, APC-(1211–2075), has β-catenin- Axin-binding sites down-regulates Glycogen synthase kinase-3β (GSK-3β) phosphorylated slightly presence either APC-(1211–2075) or...
In attempting to clarify the roles of Dvl in Wnt signaling pathway, we identified a novel protein which binds PDZ domain and named it Idax (for inhibition Axin complex).Idax competed with each other for binding Dvl.Immunocytochemical analyses showed that was localized same place as cells expression inhibited colocalization Idax.Further, Wnt-induced accumulation -catenin activation T-cell factor mammalian were suppressed by Idax.Expression Xenopus embryos induced ventralization reduction...
Although casein kinase Iε (CKIε) has been shown to regulate the Wnt signaling pathway positively, its mode of action is not clear. In this study we show that CKIε activates in co-operation with Dvl. and Axin associated different sites Dvl, Dvl interacted distinct regions on Axin. Therefore, these three proteins formed a ternary complex. Either low expression or alone did accumulate β-catenin, but their co-expression accumulated greatly. activated transcriptional activity T cell factor (Tcf)...
β-Catenin is efficiently phosphorylated by glycogen synthase kinase-3β in the Axin complex cytoplasm, resulting down-regulation. In response to Wnt, β-catenin stabilized and translocated into nucleus where it stimulates gene expression through Tcf/Lef. Here we report a novel protein, designated Duplin (for axis duplication inhibitor), which negatively regulates function of nucleus. was located bound directly Armadillo repeats β-catenin, thereby inhibiting binding Tcf β-catenin. It did not...