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T Tauchi

Publications and source records attributed to T Tauchi.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Rapidly progressive fibrosis and increased CD68-positive cells in the bone marrow at the terminal stage of adult T-cell leukemia accompanied by polycythemia vera].

We report a case of adult T-cell leukemia (ATL) accompanied by polycythemia vera (PV) in which rapid development of myelofibrosis and clinical features of hemophagocytic syndrome (HPS) were observed at the terminal stage. The patient, a 53-year-old man who was born in Oita Prefecture, Japan, was diagnosed as having PV in 1996. He had undergone venesection but had not received any chemotherapy. In June 1997, he showed systemic lymphadenopathy with positivity for serum HTLV-1 antibody (x 10,240). Pathological findings and Southern blotting analysis for detection of monoclonal integration of HTLV-1 provirus DNA in a lymph node biopsy sample revealed that he also had acute-type ATL. Although several courses of chemotherapy were transiently effective, high fever, pancytopenia, increased serum LDH, hypoproteinemia and hyperferritinemia appeared, all of which were compatible with the clinical features of HPS. In addition, cytomegalovirus infection became evident. He died of multiple organ failure with rapid progression of myelofibrosis in May 1998. Detection of both increased CD68-positive histiocytes by immunohistochemistry and iron-stained phagocytic cells in marrow biopsy specimens appeared to be helpful for diagnosis of HPS in this patient, whose marrow showed myelofibrosis with hypocellularity.

Antigens, CD↗
PubMed1999

Thrombopoietin induces an SH2-containing protein, CIS1, which binds to Mpl: involvement of the ubiquitin proteosome pathway.

The interaction of thrombopoietin (TPO) with its receptor, Mpl, triggers growth and differentiation of megakaryocytes and their progenitors. The Mpl cytoplasmic domain controls this process through src homology 2 (SH2)-containing target molecules and their receptor docking sites. A novel cytokine inducible SH2-containing protein, CIS1, has been isolated. CIS1 is induced by interleukin-2 (IL-2), IL-3, GM-CSF, and erythropoietin (EPO), but not by IL-6, granulocyte colony-stimulating factor (G-CSF), or stem cell factor. To investigate the functional domains of Mpl for induction of CIS1, we examined FDCP-2 cell lines expressing seven carboxyl truncations of the human Mpl cytoplasmic domain. We found that the box1 and box2 regions of Mpl were necessary for induction of CIS1 after TPO stimulation. CIS1 was degraded very quickly and was found to be involved in the ubiquitin-proteosome pathway. A 4-hour depletion of TPO almost completely eliminated CIS1 protein; within 1 hour after TPO stimulation, CIS1 protein reappeared as 37- and 32-kDa proteins in the wild type Mpl-expressing FDCP-2 cells. Further, CIS1 was stably associated with tyrosine-phosphorylated Mpl. The SH2 domains of CIS1, constructed as glutathione S-transferase fusion protein, bound to activated Mpl in vitro. These results suggest that CIS1 may be an important signaling component downstream of Mpl and may regulate the proliferation and differentiation of hematopoietic cells.

Animals↗
PubMed1999

[Hypereosinophilic syndrome complicated by myelofibrosis].

Hypereosinophilic syndrome (HES) with myelofibrosis was diagnosed in a 36-year-old man on the basis of bone marrow biopsy findings and clinical features. Although the patient was treated with steroid (1 mg/kg), hydroxyurea, and immunosuppressive therapy, eosinophilia persisted. Patients with HES and myelofibrosis are usually unresponsive to antineoplastic agents and/or immunosuppressants. However, cyclosporin may be an effective alternative for such patients.

Adult↗
PubMed1998

The tetramerization domain-independent Ras activation by BCR-ABL oncoprotein in hematopoietic cells.

BCR-ABL is a chimeric oncoprotein that exhibits deregulated tyrosine kinase activity and is implicated in the pathogenesis of Philadelphia chromosome-positive human leukemias. We have previously shown that BCR-ABL activates Ras signaling pathways required for transformation. To elucidate the mechanisms whereby BCR-ABL induced transformation in hematopoietic cells, we examined the biological effects of expression of a series of BCR-ABL mutants. We found that the Grb2 binding site-deleted BCR-ABL and the SH2 domain-deleted BCR-ABL, as well as the tetramerization domain-deleted BCR-ABL do not diminish the transforming properties of BCR-ABL in hematopoietic cells, although these mutations were previously shown to drastically reduce the transforming activity of BCR-ABL in fibroblasts. The tetramerization domain-deleted BCR-ABL did not induce tyrosine phosphorylation of CrkL, SHP-2, Vav and the interactions of BCR-ABL and Shc. However, Ras is activated, Shc is tyrosine phosphorylated and binds to Grb2 in the tetramerization domain-deleted BCR-ABL expressing hematopoietic cells. These results suggest that the tetramerization domain-independent Ras activation is mediated by Shc proteins and induces the transformation of hematopoietic cells.

Adaptor Proteins, Signal Transducing↗
PubMed1998

[A case report of epidural abscess due to anaerobic bacteria, producing a mass of gas].

A 54-year-old female was admitted to our hospital on May 8, 1996, for evaluation of fever and headache. Her cerebrospinal fluid showed elevation of the cell count and total protein. The thoracic and lumbar MRIs revealed abnormal gas occupying the epidural space at the sacral level, and extended as high as 9th thoracic level. The gas spread inside the iliopsoas and paraspinal muscles. Anaerobic bacteria such as Bacteroides fragilis and Peptostreptococcus productus were cultured from the spinal fluid and Bacteroides was also detected from the epidural tissues obtained during laminectomy. The infectious source was decubitus extending around the sacral bone. The combination therapy of debridement with peroxide, catheter drainage of epidural abscess, intravenous and intrathecal antibiotics, and laminectomy presented her good outcome. This is a rare case of anaerobic bacterial spinal abscess, showing epidural and intramuscular gas as a prominent feature.

Abscess↗
PubMed1997

A coiled-coil tetramerization domain of BCR-ABL is essential for the interactions of SH2-containing signal transduction molecules.

BCR-ABL is a chimeric oncoprotein that exhibits deregulated tyrosine kinase activity and is implicated in the pathogenesis of Philadelphia chromosome (Ph1)-positive leukemia. We have previously shown SH2-containing phosphotyrosine phosphatase SHP-2 forms stable complexes with BCR-ABL and Grb2 in BCR-ABL-transformed cells (Tauchi, T., Feng, G. S., Shen, R., Song, H. Y., Donner, D., Pawson, T., and Broxmeyer, H. E. (1994) J. Biol. Chem. 269, 15381-15387). To elucidate the structural requirement of BCR-ABL for the interactions with SH2-containing signaling molecules, we examined a series of BCR-ABL mutants which include the Grb2 binding site-deleted BCR-ABL (1-63 BCR/ABL), the tetramerization domain-deleted BCR-ABL (64-509 BCR/ABL), and the SH2 domain-deleted BCR-ABL (BCR/ABL deltaSH2). These BCR-ABL mutants were previously shown to reduce the transforming activity in fibroblasts. We found that the tetramerization domain-deleted BCR-ABL did not induce the tyrosine phosphorylation of SHP-2 and the interactions of BCR-ABL, SHP-2, and Grb2. In vitro kinase assays have also shown that the tetramerization domain-deleted BCR-ABL mutant did not phosphorylate GST-SHP-2 in vitro. SHP-2 was co-immunoprecipitated with phosphatidylinositol 3-kinase in BCR/ABL p210-transformed cells; however, this interaction was not observed in the tetramerization domain-deleted BCR-ABL mutant. Therefore the tetramerization domain of BCR-ABL is essential for interactions of these downstream molecules.

Cell Line↗
PubMed1996

Tyrosine 425 within the activated erythropoietin receptor binds Syp, reduces the erythropoietin required for Syp tyrosine phosphorylation, and promotes mitogenesis.

Erythropoietin (Epo), the primary in vivo stimulator of erythroid proliferation and differentiation, acts, in part, by altering the tyrosine phosphorylation levels of various intracellular signaling molecules. These phosphorylation levels are tightly regulated by both tyrosine kinases and tyrosine phosphatases. We have recently shown that the SH2 containing tyrosine phosphatase, Syp, binds directly to both the tyrosine phosphorylated form of the Epo receptor (EpoR) and to Grb2 after Epo stimulation of M07e cells engineered to express high levels of human EpoRs (T. Tauchi, et al: J Biol Chem 270:5631, 1995). To determine which tyrosine within the EpoR is responsible for binding Syp, we examined DA-3 cell lines expressing full-length mutant EpoRs bearing tyrosine to phenylalanine substitutions for each of the eight tyrosines within the intracellular domain of the EpoR. We found that: (1) all Epo-stimulated mutant EpoRs, except for the Y425F EpoR, coimmunoprecipitated with Syp; (2) all Epo-stimulated mutant EpoRs, except for the Y425F EpoR, bound to a GST-fusion protein containing both SH2 domains of Syp; (3) Jak2 could phosphorylate GST-Syp in vitro after Epo stimulation of wild-type (wt) EpoR expressing DA-3 cells; (4) Epo-stimulated tyrosine phosphorylation of Syp in vivo was markedly reduced in Y425F EpoR expressing DA-3 calls; and (5) DA-3 cells expressing the Y425F EpoR grow less well in response to Epo than wt EpoR expressing cells. These results suggest that Syp binds via its SH2 domains to phosphorylated Y425 within the EpoR and is then phosphorylated on tyrosine residues by Jak2. Moreover, Y425 in the EpoR reduces the Epo requirement for Syp tyrosine phosphorylation and promotes proliferation.

Animals↗
PubMed1996

A coiled-coil tetramerization domain of BCR-ABL is essential for the interactions of SH2-containing signal transduction molecules.

BCR-ABL is a chimeric oncoprotein that exhibits deregulated tyrosine kinase activity and is implicated in the pathogenesis of Philadelphia chromosome (ph1)-positive leukemia. We have previously shown SH2-containing phosphotyrosine phosphatase SHP-2 forms stable complexes with BCR-ABL and Grb2 in BCR-ABL transformed cells (T., Tauchi, et al. J. Biol. Chem. 269, 15381, 1994). To elucidate the structural requirement of BCR-ABL for the interactions with SH2-containing signaling molecules, we examined a series of BCR-ABL mutants which include the Grb2 binding site deleted BCR-ABL (1-63 BCR/ABL), the tetramerization domain deleted BCR-ABL (64-509 BCR/ABL), and the SH2 domain deleted BCR-ABL (BCR/ABL delta SH2). These BCR-ABL mutants were previously shown to reduce the transforming activity in fibroblasts. We found that the tetramerization domain deleted BCR-ABL did not induce the tyrosine phosphorylation of SHP-2 and the interactions of BCR-ABL, SHP-2, and Grb2. In vitro kinase assays have also shown the tetramerization domain deleted BCR-ABL mutant did not phosphorylate GST-SHP-2 in vitro. SHP-2 was co-immunoprecipitated with P13Kinase in BCR/ABL p210 transformed cells, however this interaction was not observed in the tetramerization domain deleted BCR-ABL mutant. Therefore the tetramerization domain of BCR-ABL is essential for interactions of these downstream molecules.

Fusion Proteins, bcr-abl↗
PubMed1995

Involvement of SH2-containing phosphotyrosine phosphatase Syp in erythropoietin receptor signal transduction pathways.

Erythropoietin (Epo) regulates the proliferation and differentiation of erythroid precursors. The phosphorylation of proteins at tyrosine residues is critical in the growth signaling induced by Epo. This mechanism is regulated by the activities of both protein-tyrosine kinases and protein tyrosine phosphatases. The discovery of phosphotyrosine phosphatases that contain SH2 domains suggests roles for these molecules in growth factor signaling pathways. We found that Syp, a phosphotyrosine phosphatase, widely expressed in all tissues in mammals became phosphorylated on tyrosine after stimulation with Epo in M07ER cells engineered to express high levels of human EpoR. Syp was complexed with Grb2 in Epo-stimulated M07ER cells. Direct binding between Syp and Grb2 was also observed in vitro. Furthermore, Syp appeared to bind directly to tyrosine-phosphorylated EpoR in M07ER cells. Both NH2-terminal and COOH-terminal SH2 domains of Syp, made as glutathione S-transferase fusion proteins, were able to bind to the tyrosine-phosphorylated EpoR in vitro. These results suggest that Syp may be an important signaling component downstream of the EpoR and may regulate the proliferation and differentiation of hematopoietic cells.

Adaptor Proteins, Signal Transducing↗
PubMed1995

BCR/ABL signal transduction.

A strong association between the Philadelphia chromosome (Ph1) and chronic myelogenous leukemia (CML) suggests that the Ph1 translocation plays a significant role in pathogenesis of CML. For this reason, Ph1-positive leukemias have been well studied from the molecular, clinical and cell biological perspective. In this review article, intracellular signalling events involving BCR/ABL fusion gene products are discussed in the context of the role of the Ph1 chromosome in human leukemia.

Fusion Proteins, bcr-abl↗
PubMed1995

Tyrosine phosphorylation and activation of focal adhesion kinase (p125FAK) by BCR-ABL oncoprotein.

Focal adhesion kinase (p125FAK; FAK) is a protein tyrosine kinase that is tyrosine-phosphorylated in response to v-src-mediated transformation, cell adhesion, and stimulation with neuropeptides. To elucidate a possible functional relationship between FAK and BCR-ABL oncoprotein detected in Philadelphia chromosome-positive (Ph+) leukemias, we investigated the tyrosine phosphorylation state of FAK in a murine growth factor-dependent cell line and in its stable human bcr-abl cDNA transfectant. In interleukin-3 (IL-3)-dependent NFS/N1.H7 cells, tyrosine phosphorylation of FAK was not detected after stimulation with either IL-3 or Steel factor (SLF), both of which involve Ras-mediated signaling pathways. However, stable gene transfection with p210bcr-abl cDNA into H7 cells made these cells growth factor-independent for proliferation and resulted in constitutive tyrosine phosphorylation and kinase activation of FAK. Constitutive phosphorylation and activation of FAK was also observed in all Ph+ leukemia cell lines examined--that is, K562, TS9;22, and YS9;22, which express p210BCR-ABL, and NALM-21 and OM9;22, which express p185BCR-ABL. Ph-negative (Ph-) cell lines, such as MO7e and JM, did not show any detectable tyrosine phosphorylation of FAK. FAK phosphorylation in BCR-ABL-expressing cells was inhibited in a dose-dependent manner by cytochalasin D, a reagent that disrupts the intracellular network of actin filaments. However, no suppression of kinase activity or protein expression of BCR-ABL was observed after treatment with cytochalasin D. A physical association between BCR-ABL and FAK was not apparent. These data suggest that BCR-ABL may be involved in the activation of FAK. Moreover, FAK may be distinct from components in Ras-mediated signaling cascades that are activated by stimulation of myeloid cells with various cytokines.

Animals↗
PubMed1994

The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in hematopoietic cells.

The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor, which is important for the normal development of hematopoietic cells, melanoblasts, and germ cells. Autophosphorylation of c-kit receptor on tyrosine creates binding sites for cellular src homology 2 (SH2)-containing signaling molecules. The discovery of phosphotyrosine phosphatases that contain SH2 domains suggests roles for these molecules in growth factor signaling pathways. We found that Syp, a phosphotyrosine phosphatase widely expressed in all the tissues in mammals, associates with c-kit receptor after activation with its ligand, steel factor, in the factor-dependent cell line, M07e. Both NH2-terminal and COOH-terminal SH2 domains of Syp, made as glutathione S-transferase fusion proteins, were able to bind to the activated c-kit receptor in vitro. Furthermore, Syp became marginally phosphorylated on tyrosine upon c-kit receptor activation, and tyrosine-phosphorylated Syp was found to be complexed with Grb2 in steel factor-stimulated M07e cells. Direct binding between Syp and Grb2 was also observed in vitro. Last, Ras and Raf interacts in vitro as a result of steel factor-stimulated Ras activation. These results suggest that Syp may be an important signaling component downstream of the c-kit receptor and involved in activation of the Ras signaling pathway in hematopoietic cells.

Adaptor Proteins, Signal Transducing↗