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H Yamamura

Publications and source records attributed to H Yamamura.

At least 145 records · Page 8Linked to original sources
PubMed1995

Cyclic AMP-elevating agents negatively regulate the activation of p72syk in N-formyl-methionyl-leucyl-phenylalanine receptor signaling.

Here we investigated the involvement of the non-receptor protein-tyrosine kinase p72syk in formyl methionyl-leucyl-phenylalanine (fMLP) receptor signaling. The activity of p72syk began to rise from 15 s and reached to maximum within 2-5 min after 5 microM fMLP stimulation in porcine polymorphonuclear neutrophils (PMNs). Cyclic AMP (cAMP)-elevating agents, prostaglandin E2 (PGE2) and forskolin, or dibutyryl cAMP partially suppressed p72syk activities stimulated by fMLP in PMNs. Pretreatment with an inhibitor of cAMP-dependent protein kinase abolished the suppression of the fMLP-induced p72syk activation by these cAMP-elevating agents. It was also observed that cAMP-dependent protein kinase phosphorylates p72syk on serine residues in vitro. These results indicate a possibility that cAMP-dependent protein kinase negatively regulates the activation of p72syk in fMLP-receptor signaling.

Amino Acid Sequence↗
PubMed1995

Reconstitution of interactions between tyrosine kinases and the high affinity IgE receptor which are controlled by receptor clustering.

High affinity IgE receptor (Fc epsilon RI) signaling after contact with antigen occurs in response to receptor clustering. This paper describes methodology, based on vaccinia virus driven protein expression, for probing signaling pathways and its application to Fc epsilon RI interactions with the lyn and syk tyrosine kinases. Reconstitution of the complete tetrameric Fc epsilon RI receptor, lyn and syk in a non-hematopoietic 'null' cell line is sufficient to reconstruct clustering-controlled receptor tyrosine phosphorylation and activation of syk, without apparent requirement for hematopoietic specific phosphatases. The src family kinase lyn phosphorylates Fc epsilon RI in response to receptor clustering, resulting in syk binding to the phosphorylated Fc epsilon RI. Lyn also participates in the tyrosine phosphorylation and activation of syk in a manner which is dependent on phosphorylated Fc epsilon RI. Using overexpression of active and dominant negative syk proteins in a mast cell line which naturally expresses Fc epsilon RI, we corroborate syk's role downstream of receptor phosphorylation, and demonstrate that syk SH2 domains protect receptor ITAMs from ongoing dephosphorylation. Based on these results, we propose that receptor clustering controls lyn-mediated Fc epsilon RI tyrosine phosphorylation by shifting a balance between phosphorylation and dephosphorylation towards accumulation of tyrosine phosphorylated Fc epsilon RI. Fc epsilon RI tyrosine phosphorylation functions to bring syk into a microenvironment where it becomes tyrosine phosphorylated and activated, thereby allowing clustering to indirectly control syk activity.

3T3 Cells↗
PubMed1995

Anti-CD9 monoclonal antibody activates p72syk in human platelets.

NNKY 1-19, anti-CD9 monoclonal antibody (MoAb), induced protein tyrosine phosphorylation of 125-, 97-, 75-, 64-, and 40-kDa proteins in human platelets, whereas F(ab')2 fragments of NNKY 1-19 did not, suggesting that the stimulation of Fc gamma II receptors is required for the induction of protein tyrosine phosphorylation. Tyrosine-phosphorylated proteins of 97 and 125 kDa were associated with aggregation, while NNKY 1-19-induced protein tyrosine phosphorylation was completely inhibited by prostaglandin I2 (PGI2). The activity of p72syk was assessed in immunoprecipitation kinase assays to determine at which step the signal transduction pathway leading to protein tyrosine phosphorylation was suspended. NNKY 1-19 induced a rapid and transient increase in the p72syk-associated tyrosine kinase activity that peaked at 10 s and subsided to the original level 2 min after stimulation. Coinciding with this time course, p60c-src transiently associated with p72syk. In platelets preexposed to GRGDS peptides or PGI2, NNKY 1-19 also increased the p72syk-associated tyrosine kinase activity and led to the association of p60c-src with p72syk. However, in contrast to the control without any inhibitor, the elevated tyrosine kinase activity and the associated state of the two tyrosine kinases persisted as long as 5 min after stimulation. F(ab')2 fragments of NNKY 1-19 induced changes similar to those observed with the effects of GRGDS peptides or PGI2 treatment on intact IgG NNKY 1-19 stimulation. F(ab')2 fragments of another CD9 MoAb, PMA2, had effects on p72syk essentially similar to those of NNKY 1-19. These findings suggest that the binding of anti-CD9 MoAb to CD9 on the platelet membrane per se induces an increase in the p72syk-associated tyrosine kinase activity but that Fc gamma II receptor-mediated signal(s) is required for the full activation of platelets and the appearance of tyrosine-phosphorylated proteins. The elevated intracellular cAMP level induced by PGI2 acts at a step distal to the activation of p72syk and inhibited the signal transduction pathway leading to protein tyrosine phosphorylation and aggregation. p72syk activation occurs in the absence of aggregation, but aggregation appears to reduce the elevated p72syk activity induced by anti-CD9 MoAb.

Antibodies, Monoclonal↗
PubMed1995

Morphological classification of retinal ganglion cells in mice.

Mice have been used for extensive studies on optic nerves and retinal ganglion cells, but mouse retinal ganglion cells have not been classified morphologically. In the present study, normally placed retinal ganglion cells and displaced retinal ganglion cells in pigmented and albino mice were classified morphologically using horseradish peroxidase. These cells were classified into three types according to the sizes of the soma and the dendritic field: type I cells, large soma and large dendritic field; type II cells, small-to-medium soma and small dendritic field; and type III cells, small-to-medium soma and large dendritic field. Some ganglion cells had both symmetric and asymmetric cells. Each type was further subdivided according to the termination level of dendrites in the inner plexiform layer and the dendritic branching pattern. Except for type III displaced ganglion cells, dendrites of the normally placed ganglion cells and the displaced ganglion cells ramify in the outer two-fifths of the inner plexiform layer (sublamina a) or the inner three-fifths of the inner plexiform layer (sublamina b). Type III displaced ganglion cells ramify only in sublamina a. Dendrites of some normally placed type I ganglion cells ramify in both sublaminae. Displaced biplexiform cells were observed, the dendrites of which ramify in both the inner and the outer plexiform layers. All cell types were found in both mouse strains.

Animals↗
PubMed1995

Activation and tyrosine phosphorylation of p72syk as well as calcium mobilization after hydrogen peroxide stimulation in peripheral blood lymphocytes.

To determine the regulatory role of p72syk in lymphocyte activation, peripheral blood lymphocytes were treated with 10 mM hydrogen peroxide. Hydrogen peroxide induced a rapid elevation of p72syk activity (4-6-fold) and a dramatic increase in tyrosine phosphorylation of a number of cellular proteins, including phospholipase C gamma 1 (PLC gamma 1) and p72syk. Monoclonal antibodies to PLC gamma 1 co-precipitated p72syk from hydrogen peroxide-stimulated cell lysates, but not from unstimulated cell lysates. Furthermore, we observed a rise in intracellular Ca2+, corresponding to the combination of extracellular Ca2+ influx and the release from intracellular Ca2+ stores. Extracellular Ca2+ influx was necessary for the sustenance of p72syk activity, but not for the initiation of p72syk activation induced by hydrogen peroxide. Taken together, these data suggested that one possible role of p72syk was to activate PLC gamma 1, at least in part through tyrosine phosphorylation, and then to trigger calcium mobilization in pig peripheral blood lymphocytes in response to hydrogen peroxide stimulation.

Animals↗
PubMed1995

A requirement for Syk in the activation of the microtubule-associated protein kinase/phospholipase A2 pathway by Fc epsilon R1 is not shared by a G protein-coupled receptor.

Stimulation of the mast cell line, RBL-2H3, with antigen via the tetrameric (alpha beta gamma 2) immunoglobulin E receptor (Fc epsilon R1) leads to the activation of cytosolic phospholipase A2 and the release of arachidonic acid. This pathway is dependent on the activation of the mitogen-activated protein (MAP) kinase. In this paper, we show that the MAP kinase/cytosolic phospholipase A2 pathway is linked to Fc epsilon R1 via the cytosolic tyrosine kinase, Syk, and that the GDP/GTP exchange factor, Vav, might be one candidate for accomplishing this link. Cross-linking of transmembrane chimeras containing the Fc epsilon R1 gamma motif, which is known to activate Syk, results in the tyrosine phosphorylation of Vav, activation of MAP kinase, and release of arachidonic acid. Cross-linking of chimeras containing the Fc epsilon R1 beta motif does not cause these events. Furthermore, stimulation of these events by antigen is enhanced by transient overexpression of a wild-type form of Syk and blocked by overexpression of a dominant negative form of Syk. By contrast, stimulation via the transfected, G protein-coupled, muscarinic m1 receptor is not influenced by either form of Syk and does not result in tyrosine phosphorylation of Vav. These data establish unequivocally that the two types of receptor are independently linked to the two types of receptor are independently linked to the MAP kinase/cytosolic phospholipase A2 pathway and demonstrate the existence of the Fc epsilon R1-Syk-MAP kinase pathway.

Animals↗
PubMed1995

Tyrosine phosphorylation of Shc is mediated through Lyn and Syk in B cell receptor signaling.

Shc protein is tyrosine phosphorylated upon B cell receptor (BCR) activation and after its phosphorylation interacts with the adaptor protein Grb2. In turn, Grb2 interacts with the guanine nucleotide exchange factor for Ras, mSOS. Several protein-tyrosine kinases (PTKs) participate in BCR signaling. However, it is not clear which PTK is involved in the phosphorylation of Shc, resulting in coupling to the Ras pathway. Tyrosine phosphorylation of Shc and its association with Grb2 were profoundly reduced in both Lyn- and Syk-deficient B cells upon BCR stimulation. Furthermore, kinase activity of these PTKs was required for phosphorylation of Shc. Shc interacted with Syk in B cells. This interaction and the requirement of Syk kinase activity for phosphorylation of Shc were also demonstrated by cotransfection in COS cells. Because Lyn is required for activation of Syk upon receptor stimulation, our results suggest that the Lyn-activated Syk phosphorylates Shc during BCR signaling.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Mechanism of histamine release by endothelin-1 distinct from that by antigen in mouse bone marrow-derived mast cells.

The mechanisms of endothelin-1-induced histamine release were examined and compared with those responsible for antigen-induced release by using passively sensitized mouse bone marrow-derived mast cells and various drugs that may influence histamine release. The following results were obtained: (1) Although islet-activating protein potently inhibited endothelin-1-induced histamine release, it did not affect the antigen-induced release. (2) Histamine release induced by endothelin-1 was relatively more sensitive to ethylenediaminetetraacetic acid than that induced by antigen, although extracellular Ca2+ is a requisite for both types of the release. (3) (8R*, 9S*, 11S*)-(-)-9- hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H, 11H-2, 7b,11a-triazadibenzo[a,g]cycloocta[c,d,e]trinden-1-one and (8R*, 9S*, 11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-14-n-propoxy-2,3,9,10-tet rahydro - 8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo[a,g]cycloocta-[c ,d,e] trinden-1-one, which possibly inhibit protein kinases, strongly inhibited antigen-induced histamine release, while these drugs alone did not inhibit endothelin-1-induced release. (4) Staurosporine, a non-selective protein kinase inhibitor, prevented the elevation of cytosolic Ca2+ concentrations induced by antigen, whereas that induced by endothelin-1 was not influenced; histamine release induced by either stimulus was greatly inhibited by the drug. These results indicate and/or suggest that some biological events induced by endothelin-1 leading to histamine release are different from those involved in the histamine release induced by antigen.

Alkaloids↗
PubMed1995

Effects of sodium thiosulfate on the pharmacokinetics of unchanged cisplatin and on the distribution of platinum species in rat kidney: protective mechanism against cisplatin nephrotoxicity.

To investigate the mechanism underlying the protective effect against cisplatin (CDDP) nephrotoxicity of its antidote, sodium thiosulfate (STS), the effects of STS on the pharmacokinetics of unchanged CDDP and on the distribution of unchanged CDDP and high and low molecular mass metabolites (fixed and mobile metabolites) in the kidney 1 min after a bolus injection of CDDP (5 mg/kg) to rats were studied. A decrease in the plasma concentration of unchanged CDDP and an increase in the plasma concentration of mobile metabolites were observed in the rats after the bolus injection of CDDP in combination with STS infusion for 30 min (1200 mg/kg). Although STS accelerated platinum excretion during the first 10 min after CDDP injection, unchanged CDDP was not excreted in the urine in the STS-treated rats. Total kidney platinum 1 min after the bolus injection of CDDP was detected mainly as unchanged CDDP (86% of the total platinum) in the rats given CDDP alone. However, in the STS-treated rats, the total kidney platinum was decreased to 62% of the level in the rats given CDDP alone, and the platinum species detected in the kidney were mainly mobile metabolites. Only 24% of the total kidney platinum was detected as unchanged CDDP in the STS-treated rats. The loss of body weight and increases in BUN and serum creatinine levels usually observed after a bolus injection of CDDP were completely prevented by STS coadministration. The present study provides information about unchanged CDDP pharmacokinetics and the distribution of unchanged CDDP and some of its generic metabolites in the kidney when STS is coadministered as an antidote. These results show that the protective effect of STS against CDDP nephrotoxicity can be attributed to the formation of inactive mobile metabolites by a direct reaction between unchanged CDDP and STS in the systemic circulation, resulting in a reduction in the amount of unchanged CDDP in the kidney.

Analysis of Variance↗
PubMed1995

Protein tyrosine kinase Syk is associated with and activated by the IL-2 receptor: possible link with the c-myc induction pathway.

The IL-2 receptor (IL-2R) consists of three subunits, the IL-2R alpha, IL-2R beta, and IL-2R gamma chains. The IL-2-induced proliferative signals emanate from the cytoplasmic domains of IL-2R beta and IL-2R gamma, but the nature and function of the signaling molecules that transmit these signals are not fully understood. Here, we report that Syk protein tyrosine kinase (PTK) is physically associated with IL-2R in peripheral blood lymphocytes. cDNA expression studies further revealed that this association is critical for the IL-2-induced activation of Syk PTK, which occurs primarily via the serine-rich region of the IL-2R beta chain, which is essential for proliferative signal transmission. Furthermore, we provide evidence that in the hematopoietic cell line, BAF-B03, the activation of Syk PTK results in the induction of the c-myc gene, an event critical for the cell proliferation. Thus, Syk PTK may be a critical integral member of the signaling molecules engaged by the IL-2R.

Adult↗
PubMed1995

Possible involvement of protein-tyrosine kinases such as p72syk in the disc-sphere change response of porcine platelets.

We previously reported that p72syk, a non-receptor tyrosine kinase, was activated maximally at 10 s after thrombin or thromboxane A2 stimulation, even in platelets that were not allowed to aggregate [Taniguchi et al. (1993) J. Biol. Chem. 268, 2277-2279; Maeda et al. (1993) Biochem. Biophys. Res. Commun. 197, 62-67]. Then, the change in the shape of porcine platelets induced by the thromboxane A2 analogue, STA2, and the role of protein-tyrosine kinases including p72syk in this response were evaluated, using the shape-change parameter. We show that p72syk activation is correlated with the disc-sphere change in a time- and dose-dependent manner following stimulation by STA2. Tyrphostin B44, a potent protein-tyrosine kinase inhibitor, reduced the thromboxane A2-evoked p72syk activation and the disc-sphere change in a dose-dependent manner. Furthermore, the translocation of p72syk to the cytoskeleton-rich fraction and an increase in the tyrosine phosphorylation of an about 120 kDa protein were observed during the disc-sphere change induced by STA2. These lines of evidence suggest that the activation of protein-tyrosine kinases such as p72syk may be involved in the disc-sphere change response in thromboxane A2-stimulated porcine platelets.

Animals↗
PubMed1995

Syk and Lyn are involved in radiation-induced signaling, but inactivation of Syk or Lyn alone is not sufficient to prevent radiation-induced apoptosis.

Radiation-induced biochemical events that mediate the intracellular signal transduction leading to cell apoptosis are largely unknown. Limited evidence suggests the possible involvement of one or more protein-tyrosine kinases (PTKs) in radiation-induced cellular responses, including apoptosis. However, so far, a PTK(s) responsible for the radiation-induced tyrosine phosphorylation of cellular substrates has not been identified and the role of the PTK(s) in the radiation-induced apoptosis remains unclear. To examine the roles of Syk and Lyn in radiation-induced signal transduction and radiation-induced apoptosis, we analyzed Syk-deficient or Lyn-deficient DT40 B cells along with wild-type cells following radiation. When DT40 B cells were exposed to radiation, the activity of Syk kinase dramatically increased and reached a maximum with 0.25 Grays (Gy) (15 s), and then decreased, whereas Lyn kinase activity increased and reached a maximum with a dose of 1.00 Gy (1 min). However, an apparent difference was not observed in radiation-induced apoptosis among wild-type, Syk-deficient, and Lyn-deficient DT40 B cells. These results indicate that Syk and Lyn kinases are involved in radiation-induced signal transduction, with different kinetics. In addition, our results revealed that functional inactivation of Syk or Lyn alone is not sufficient to prevent radiation-induced apoptosis. Thus, it is suggested that the activation of Syk or Lyn kinase alone may be sufficient to mediate the radiation-induced apoptosis in DT40 B cells, or both kinases may not be required for this biological process.

Animals↗
PubMed1995

Purification and phosphorylation of a M(r) 25,000 protein, an effective phosphate acceptor for casein kinase II and protein kinase C, detected in the cytosolic fraction of Xenopus laevis oocytes.

A common and effective phosphate acceptor protein for casein kinase II and Ca(2+)-phospholipid-dependent protein kinase (protein kinase C) was purified to near homogeneity from the cytosolic fraction of Xenopus laevis oocytes. Its molecular mass was estimated to be approximately 25,000 by SDS-polyacrylamide slab gel electrophoresis and gel filtration analyses. About 1 and 2 mol of phosphate were incorporated per mol of this protein with casein kinase II and protein kinase C, respectively, and the phosphorylated amino acid was identified as serine irrespective of the protein kinase employed. The Km values were calculated to be 1 and 0.5 microM for this M(r) 25,000 protein with casein kinase II and protein kinase C, respectively. However, this protein was a relatively poor substrate for casein kinase I and did not serve as one for cAMP-dependent protein kinase. The amino acid sequence of its amino-terminal region suggests that this protein is a newly identified substrate for these two protein serine/threonine kinases.

Amino Acid Sequence↗
PubMed1995

Phosphorylation of HS1, GAP-associated p190 and a novel GAP-associated p60 protein by cross-linking of Fc gamma RIIIA.

Human Fc gamma receptor IIIA (hFc gamma RIIIA) cDNA was introduced into mouse macrophage/monocyte cell line P388D1, and several stable cell clones expressing hFc gamma RIIIA were isolated. This facilitated the study of the biological function of Fc gamma RIIIA in monocytes/macrophages. The cloned cells showed the high phagocytic activity mediated by hFc gamma-RIIIA, while the original P388D1 cells did not. In order to examine the phosphorylation of proteins involved in hFc gamma RIIIA signal transduction, these receptors were stimulated by cross-linking. The cross-linking of hFc gamma RIIIA induced a rapid increase in tyrosine phosphorylation of several proteins, including PLC-gamma 1, Syk, HS1, and p21rasGAP-associated p190 and p60 proteins. Immunoblotting with a polyclonal antibody specific for the GAP-associated p62 protein, which was originally found in fibroblasts and is homologous with an RNA-binding protein, revealed that the p60 phosphorylated after cross-linking of hFc gamma RIIIA seemed to represent a novel GAP-associated protein unrelated to the known GAP-associated p62 protein, which was also present in the P388D1 cells.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Lithium delays the radiation-induced apoptotic process in external granule cells of mouse cerebellum.

Proliferating cells of the external granular layer (EGL) in the developing cerebellum are highly sensitive to ionizing radiation. We examined the effect of lithium, an inhibitor of intracellular signaling, on the manifestation of radiation-induced apoptosis. Newborn mice were exposed to 0.5 Gy gamma-irradiation alone, or first were treated with lithium (10 mumol/g, SC) then given 0.5 Gy irradiation 2 hr later. The EGL was examined histologically for apoptosis at various times after treatment. Apoptotic cells increased rapidly, peaked (about 14%) 6 hr after irradiation, then decreased gradually to the control level by 24 hr. Prior treatment with lithium delayed the manifestation of apoptosis, the peak appearing at 12 hr. The disappearance of dead cells was delayed for about one day. The lithium concentration in the whole brain increased rapidly, being 30 micrograms/g at the time of irradiation and remaining at more than 40 micrograms/g for 40 hr. Lithium is reported to inhibit guanine-nucleotide binding to G proteins as well as phosphoinositide turnover. Of the variety of lesions induced by radiation, DNA double strand breaks are the most important source of cell lethality. The present findings, however, suggest that cyclic AMP-mediated and/or phosphoinositidemediated signaling systems regulate radiation-induced apoptosis.

Animals↗
PubMed1995

[Intravenous single dose toxicity of iodixanol, a new nonionic iso-osmolar contrast medium, in mice, rats and monkeys].

The single-dose intravenous toxicities of iodixanol, a new nonionic iso-osmolar contrast medium, were investigated in mice, rats and monkeys. The LD50 values were estimated to be 17.9 gI/kg for male mice and 16.2 gI/kg for female mice, 18.8 gI/kg for male rats and 22.0 gI/kg for female rats, and more than 10.0 gI/kg for monkeys. There was no marked sex difference in mice or rats, nor any significant difference observed between these two rodent species. Decrease in spontaneous locomotor activity, ptosis, respiratory depression and abdominal posture were observed in many mice and rats. These signs disappeared mostly by 8 days after dosing in surviving animals. Death occurred between immediately and 4 days after dosing in mice, and between immediately and 14 days after dosing in rats. Transient depression of body weight gain was observed in the surviving mice and rats by 7 days after dosing. Histological examinations revealed congestion or hemorrhage in the renal medulla, vacuolation or necrosis of the renal proximal tubular epithelium in mice and rats that died and vacuolation of the renal proximal tubular epithelium in surviving rats. There were no significant treatment-related changes in the laboratory and pathological examinations in monkeys.

Animals↗
PubMed1995

Effects of different doses of gamma-radiation on the developing brain of mice.

Morphogenetic changes in the developing brain induced by doses of 60Co gamma-irradiation ranging from 0 to 1.5 Gy on day 13 of pregnancy (E13) were studied in 6-week-old mice. Dose-related reductions in brain weight and cortical thickness (field 3 of Caviness) were significant for all irradiated groups, but abnormal cortical architecture was evident only in mice exposed to 1.0 and 1.5 Gy. Ectopic gray matter, enlarged lateral ventricles, and the absence of trunks from the corpus callosum were observed respectively in 23%, 30% and 10% of the mice exposed to 1.0 Gy, but these anomalies rose to 90%, 82% and 35% of the mice, respectively, when 1.5 Gy irradiation was applied. Brain malformations identical to the small heads and ectopic gray matter typically observed among atomic bomb survivors were reproduced in mice exposed to 1.5 Gy irradiation on E13.

Abnormalities, Radiation-Induced↗