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Showing papers by "Toshio Suda published in 1996"


Journal ArticleDOI
01 Feb 1996-Blood
TL;DR: The results indicate that functional loss of the gamma chain causes significant effects on the immunological system in mice.

265 citations


Journal ArticleDOI
01 May 1996-Blood
TL;DR: The results indicate that CD34 plays an important role in eosinophil trafficking into the lung and an additional molecule(s) that might be involved in leukocyte trafficking is identified.

136 citations


Journal ArticleDOI
TL;DR: These results demonstrate that positive or negative signals toward cell growth are generated through the multifunctional docking site and suggest the involvement of p61 and p65 as well as JNK in apoptosis, the first evidence for apoptosis via a receptor tyrosine kinase.
Abstract: STK/RON tyrosine kinase, a member of the hepatocyte growth factor (HGF) receptor family, is a receptor for macrophage-stimulating protein (MSP). To examine the STK/RON signalling pathway, we generated STK/ RON transfectants showing opposite features in growth. STK/RON-expressing Ba/F3 pro-B cells (BaF/STK) exhibited MSP-dependent growth, whereas STK/ RON-expressing mouse erythroleukaemia cells (MEL/ STK) displayed MSP-induced apoptosis. This apoptosis was accompanied by the prolonged activation of c-Jun N-terminal kinase (JNK), which has recently been implicated in the initiation of apoptosis. Co-immunoprecipitation analyses showed that autophosphorylated STK/RON associated with PLC-gamma, P13-kinase, Shc and Grb2 in both transfectants. However, major tyrosine-phosphorylated proteins, p61 and p65, specifically associated with STK/RON in MEL/STK cells. Mutations at two C-terminal tyrosine residues, Y1330 and Y1337, in the counterpart of the multifunctional docking site of the HGF receptor abolished both MSP-induced growth and apoptosis. Analyses of these mutants and in vitro association revealed that signalling proteins including p61 and p65 directly bound to the phosphotyrosines in the multifunctional docking site. These results demonstrate that positive or negative signals toward cell growth are generated through the multifunctional docking site and suggest the involvement of p61 and p65 as well as JNK in apoptosis. Our findings provide the first evidence for apoptosis via a receptor tyrosine kinase.

135 citations


Journal ArticleDOI
TL;DR: It is reported that MSP induced proliferation of murine primary keratinocytes and established keratinocyte cell lines in a concentration-dependent manner and Herbimycin A, a protein tyrosine kinase inhibitor, blocked MSP-mediated phosphorylation of the STK receptor as well as proliferation of Keratinocytes, suggesting the importance of tyrosin kinase activity for transduction of the message delivered by MSP.

107 citations


Journal ArticleDOI
TL;DR: In situ hybridization revealed that Cek8, a member of the eph family, was specifically expressed on motoneurons at the brachial and lumbar segments of the spinal cord which innervate limb muscles, and disappeared after the naturally occurring cell death period.

105 citations


Journal Article
15 Aug 1996-Oncogene
TL;DR: Findings suggest the involvement of HTK-HTKL system in the proliferation ofHTK+ hematopoietic progenitor cells in the hematopolietic environment.
Abstract: HTK is a receptor tyrosine kinase that belongs to the Eph subfamily. An extensive screening using BIAcore system revealed that a colon cancer cell line, C-1, expressed the ligand for HTK. From the conditioned medium of C-1 cells, a soluble form of ligand was purified by receptor affinity chromatography, and the isolation of full-length cDNA revealed that this ligand is identical to the human HTK ligand (HTKL) previously reported. HTK receptor tyrosine phosphorylation was induced by membrane-bound or clustered soluble HTKL but not by unclustered soluble HTKL, indicating that HTKL requires cell-to-cell interaction for receptor activation. Binding analysis demonstrated that HTKL binds to HTK with a much higher affinity (Kd: 1.23 nM) than the other transmembrane-type ligand for Eph family, LERK-2/ELKL (Kd: 135 nM). The expression of HTK in cord blood cells was upregulated after the culture in the presence of stem cell factor. Clustered soluble HTKL stimulated the proliferation of sorted HTK+ cord blood cells and a hematopoietic cell line, UT-7/EPO from which HTK was isolated. These findings suggest the involvement of HTK-HTKL system in the proliferation of HTK+ hematopoietic progenitor cells in the hematopoietic environment.

94 citations


Journal ArticleDOI
01 May 1996-Blood
TL;DR: Findings suggest that by involving src kinase, the MSP/STK signal transduction pathway induces rapid cytoskeletal reorganization in osteoclasts and facilitates bone resorption by osteoclast.

85 citations


Journal ArticleDOI
01 Jan 1996-Blood
TL;DR: Findings indicate that TIE has a unique spectrum of expression in primitive hematopoietic stem cells and B cells, and may establish a novel regulatory pathway not only in early hematoiesis, but also in the differentiation and/or proliferation of B cells.

66 citations


Journal ArticleDOI
15 Jun 1996-Blood
TL;DR: It is reported here that CD34+ hematopoietic progenitor cells of P NH-BM yielded blood cells of three lineages with PNH phenotype alone when transplanted into sublethally irradiated severe combined immunedeficient mice, indicating the intrinsic growth abnormality of PNH clone.

54 citations


Journal ArticleDOI
TL;DR: The results suggest that CHK/HYL might not have the same function as CSK, although CSK negatively regulates Src family kinases in cultured bone marrow cells.

36 citations


Journal ArticleDOI
01 Feb 1996-Blood
TL;DR: A unique cooperation between p59fyn and p125FAK in CD4+CD8+ T-cell development is suggested in thymocytes with atrophy of the thymic cortex.

Journal ArticleDOI
TL;DR: It is suggested that locally produced MSP may play a vital role in germ cell-germ cell interaction during spermatogenesis as well as in the acquisition of sperm motility and/or fertilizing capacity in the epididymis.

Journal ArticleDOI
TL;DR: Forward-angle coincident electroproduction cross sections of charged pions from 3He have been measured at electron energies E0 ­ 855, 675, 600, and 555 MeV in terms of a microscopic model, including pole terms, final state rescattering and produced and preformedD resonances.
Abstract: Forward-angle coincident electroproduction cross sections of charged pions from ${}^{3}\mathrm{He}$ have been measured at electron energies ${E}_{0}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}855$, 675, 600, and 555 MeV. The overall features of the data for energy transfers of $\ensuremath{\omega}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}370$ to 430 MeV with pions detected along the momentum transfer axis are reproduced in terms of a microscopic model, including pole terms, final state rescattering and produced and preformed $\ensuremath{\Delta}$ resonances. Separation of the cross section into its longitudinal and transverse parts was performed at ${Q}^{2}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}0.045\phantom{\rule{0ex}{0ex}}(\mathrm{GeV}/c{)}^{2}$. The longitudinal part of the cross section in the ${\ensuremath{\pi}}^{+}$ channel does not contradict with the assumption of a preformed ${\ensuremath{\Delta}}^{++}$.

Journal Article
04 Jul 1996-Oncogene
TL;DR: 'knocked-in' the csk gene, a negative regulator of SRC-family kinases, into fyn locus to challenge the problem of redundant functions among Src- family kinases in mice displayed atrophy of the thymic cortex and impaired development of CD4+ CD8+ thymocytes.
Abstract: p59fyn is one of the Src-family kinases thought to play an important role in signaling through T cell receptor. However, Fyn deficiency has caused no overt defects in vivo on T cell development, nor has it caused any changes in the phosphorylation status of molecules such as ZAP-70 which have been proposed as p59fyn substrates. This could be explained as being due to compensation of Fyn deficiency by other Src-family kinases. Here, we have 'knocked-in' the csk gene, a negative regulator of Src-family kinases, into fyn locus to challenge the problem of redundant functions among Src-family kinases. The csk-'knock-in' mice displayed atrophy of the thymic cortex and impaired development of CD4+ CD8+ thymocytes. This was concomitant with decrease in tyrosine phosphorylation of ZAP-70 and p120cbl.

Book ChapterDOI
01 Jan 1996
TL;DR: FACS analysis of human bone marrow mononuclear cells showed that HTK receptor was expressed in CD34lowc-KIT+ hematopoietic progenitor cell fraction, suggesting the involvement of HTKL in the differentiation and/or proliferation of these progenitors cells.
Abstract: HTK is a receptor tyrosine kinase (RTK) which belongs to the Eph subfamily of RTK. Using a BlAcore, a surface plasmon resonance detection system, it was determined that a colon cancer cell line C-1 expressed HTK ligand (HTKL). From the conditioned medium of C-1 cells, a soluble form of HTKL was purified by receptor affinity chromatography. The N-terminal amino acid sequence of purified HTKL was determined and the full-length cDNA of HTKL was isolated from a C-1 cell cDNA library. HTKL is a type I transmembrane protein which consists of 333 amino acids. HTK receptor tyrosine phosphorylation was induced by membrane-bound or clustered soluble ligands but not by unclustered soluble ligands, indicating that HTKL requires cell-to-cell interaction for receptor phosphorylation. FACS analysis of human bone marrow mononuclear cells showed that HTK receptor was expressed in CD34lowc-KIT+ hematopoietic progenitor cell fraction. These findings suggest the interaction of hematopoietic progenitor cells with HTKL-expressing cells in bone marrow and the involvement of HTKL in the differentiation and/or proliferation of these progenitor cells.