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Additional Pathways (additional + pathway)
Selected AbstractsFunctional dissection of transformation by c-Src and v-SrcGENES TO CELLS, Issue 1 2008Chitose Oneyama The c-src proto-oncogene product, c-Src, is frequently over-expressed and activated in various human malignant cancers, implicating a role for c-Src in cancer progression. To verify the role of c-Src, we analyzed the transforming ability of c-Src in mouse embryonic fibroblasts that lack Csk, a negative regulator of Src family kinases. Although Csk deficiency is not sufficient for cell transformation, c-Src over-expression induced characteristic transformed phenotypes including anchorage-independent growth and tumorigenecity. These phenotypes were dose-dependently inhibited by the re-expression of Csk, indicating that there is a certain threshold for c-Src transformation, which is determined by the c-Src : Csk ratio. In contrast to v-Src, c-Src induced the phosphorylation of a limited number of cellular proteins and elicited a restricted change in gene expression profiles. The activation of some critical targets for v-Src transformation, such as STAT3, was not significantly induced by c-Src transformation. Several genes that are involved in cancer progression, that is, cyclin D1 and HIF-1,, were induced by v-Src, but not by c-Src. Furthermore, v-Src tumors exhibited aggressive growth and extensive angiogenesis, while c-Src tumors grew more slowly accompanied by the induction of hematomas. These findings demonstrate that c-Src has the potential to induce cell transformation, but it requires coordination with an additional pathway(s) to promote tumor progression in vivo. [source] 70,S Ribosomes Bind to Shine,Dalgarno Sequences without Required DissociationsCHEMBIOCHEM, Issue 6 2008Shuntaro Takahashi Dr. To dissociate or not to dissociate. Although it is thought that the intact 70S ribosome must dissociate into 30S and 50S subunit and the dissociated 30S subunit binds to a Shine,Dalgarno (SD) sequence of mRNA in the first step of the initiation translation, we found an additional pathway that the intact 70S ribosome can bind directly to mRNA SD sequences without a required dissociation. [source] The chemotaxis defect of Shwachman-Diamond Syndrome leukocytesCYTOSKELETON, Issue 3 2004Vesna Stepanovic Abstract Shwachman-Diamond Syndrome (SDS) is a rare autosomal recessive, multisystem disorder presenting in childhood with intermittent neutropenia and pancreatic insufficiency. It is characterized by recurrent infections independent of neutropenia, suggesting a functional neutrophil defect. While mutations at a single gene locus (SBDS) appear to be responsible for SDS in a majority of patients, the function of that gene and a specific defect in SDS neutrophil behavior have not been elucidated. Therefore, employing 2D and 3D computer-assisted motion analysis systems, we have analyzed the basic motile behavior and chemotactic responsiveness of individual polymorphonuclear leukocytes (PMNs) of 14 clinically diagnosed SDS patients. It is demonstrated that the basic motile behavior of SDS PMNs is normal in the absence of chemoattractant, that SDS PMNs respond normally to increasing and decreasing temporal gradients of the chemoattractant fMLP, and that SDS PMNs exhibit a normal chemokinetic response to a spatial gradient of fMLP. fMLP receptors were also distributed uniformly through the plasma membrane of SDS PMNs as in control PMNs. SDS PMNs, however, were incapable of orienting in and chemotaxing up a spatial gradient of fMLP. This unique defect in orientation was manifested by the PMNs of every SDS patient tested. The PMNs of an SDS patient who had received an allogenic hematopoietic stem cell transplant, as well as PMNs from a cystic fibrosis patient, oriented normally. These results suggest that the defect in SDS PMNs is in a specific pathway emanating from the fMLP receptor that is involved exclusively in regulating orientation in response to a spatial gradient of fMLP. This pathway must function in parallel with additional pathways, intact in SDS patients, that emanate from the fMLP receptor and regulate responses to temporal rather than spatial changes in receptor occupancy. Cell Motil. Cytoskeleton 57:158,174, 2004. © 2004 Wiley-Liss, Inc. [source] Rapamycin impairs trabecular bone acquisition from high-dose but not low-dose intermittent parathyroid hormone treatmentJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2009P.J. Niziolek The osteo-anabolic effects of intermittent parathyroid hormone (PTH) treatment require insulin-like growth factor (IGF) signaling through the IGF-I receptor. A major downstream target of the IGF-I receptor (via Akt) is the mammalian target of rapamycin (mTOR), a kinase involved in protein synthesis. We investigated whether the bone-building effects of intermittent PTH require functional mTOR signaling. Mice were treated with daily PTH 1,34 (0, 10, 30, or 90,µg/kg) for 6 weeks in the presence or absence of rapamycin, a selective inhibitor of mTOR. We found that all PTH doses were effective in enhancing bone mass, whether rapamycin was present or not. Rapamycin had little to no effect on the anabolic response at low (10,µg) PTH doses, small effects in a minority of anabolic measures at moderate doses (30,µg), but the anabolic effects of high-dose PTH (90,µg) were consistently and significantly suppressed by rapamycin (,4,36% reduction). Serum levels of Trap5b, a marker of resorption, were significantly enhanced by rapamycin, but these effects were observed whether PTH was absent or present. Our data suggest that intermittent PTH, particularly at lower doses, is effective in building bone mass in the presence of rapamycin. However, the full anabolic effects of higher doses of PTH are significantly suppressed by rapamycin, suggesting that PTH might normally activate additional pathways (including mTOR) for its enhanced high-dose anabolic effects. Clinical doses of intermittent PTH could be an effective treatment for maintaining or increasing bone mass among patients taking rapamycin analogs for unrelated health issues. J. Cell. Physiol. 221: 579,585, 2009. © 2009 Wiley-Liss, Inc. [source] Photoamination of 1-hydroxyanthraquinone in a water-acetonitrile mixed solventJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 4 2009Masahiro Tajima Abstract We investigated the photoamination kinetics of 1-hydroxyanthraquinones in a water-acetonitrile mixed solvent by stationary light irradiation. The progression of the reaction under an inert atmosphere demonstrated the existence of additional reaction pathways. The excited triplet state of the base form of the 1-hydroxyanthraquinones was found to be responsible for the additional pathways. On the other hand, the same reaction under air involved an attack of the amine-derived radical species (aminium and amino radicals) on the ground state of the 1-hydroxyanthraquinones. One of the pathways preferentially led to 2-amination, and the other led exclusively to 4-amination. Results also indicate the attainment of an equilibrium state between the aminium and amino radicals. Copyright © 2008 John Wiley & Sons, Ltd. [source] New Results on the Photochemistry of Biopterin and Neopterin in Aqueous SolutionPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2009Mariana Vignoni New photochemical studies of the reactivity of biopterin (BPT) and neopterin (NPT) in acidic (pH = 5.5) and alkaline (pH = 10.5) aqueous solutions at 350 nm and room temperature were performed. The photochemical properties of BPT are of particular interest because the photolysis of this compound takes place in the white skin patches of patients affected by vitiligo. The photochemical reactions were followed by UV/VIS spectrophotometry, HPLC, electrochemical measurement of dissolved O2 and enzymatic methods for hydrogen peroxide (H2O2) and superoxide anion (O2,,) determinations. When BPT or NPT are exposed to UVA radiation, a red intermediate, very likely 6-formyl-5,8-dihydropterin, is generated in an O2 -independent process. That product is rapidly oxidized on admission of O2 to yield 6-formylpterin and H2O2. When the photolysis takes place in aerobic conditions, no additional pathways exist. On the other hand, in the absence of O2, the intermediate generated is not stable and leads to the formation of many products. O2,, is also generated during photo-oxidation of BPT and NPT. The quantum yields of reactant consumption depends on the O2 concentration: the higher the O2 concentration, the lower the quantum yields. This behavior is discussed in connection with the excited state of the pterins. [source] | |||||||||||||