50 research outputs found

    Phosphoinositide-dependent protein kinase-1 (PDK1)-independent activation of the protein kinase C substrate, protein kinase D

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    Phosphoinoisitide dependent kinase l (PDK1) is proposed to phosphorylate a key threonine residue within the catalytic domain of the protein kinase C (PKC) superfamily that controls the stability and catalytic competence of these kinases. Hence, in PDK1-null embryonic stem cells intracellular levels of PKCalpha, PKCbeta1, PKCgamma, and PKCepsilon are strikingly reduced. Although PDK1-null cells have reduced endogenous PKC levels they are not completely devoid of PKCs and the integrity of downstream PKC effector pathways in the absence of PDK1 has not been determined. In the present report, the PDK1 requirement for controlling the phosphorylation and activity of a well characterised substrate for PKCs, the serine kinase protein kinase D, has been examined. The data show that in embryonic stem cells and thymocytes loss of PDK1 does not prevent PKC-mediated phosphorylation and activation of protein kinase D. These results reveal that loss of PDK1 does not functionally inactivate all PKC-mediated signal transduction

    Notch-induced T cell development requires phosphoinositide-dependent kinase 1

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    Phosphoinositide-dependent kinase l (PDK1) phosphorylates and activates multiple AGC serine kinases, including protein kinase B (PKB), p70Ribosomal S6 kinase (S6K) and p90Ribosomal S6 kinase (RSK). PDK1 is required for thymocyte differentiation and proliferation, and herein, we explore the molecular basis for these essential functions of PDK1 in T lymphocyte development. A key finding is that PDK1 is required for the expression of key nutrient receptors in T cell progenitors: CD71 the transferrin receptor and CD98 a subunit of L-amino acid transporters. PDK1 is also essential for Notch-mediated trophic and proliferative responses in thymocytes. A PDK1 mutant PDK1 L155E, which supports activation of PKB but no other AGC kinases, can restore CD71 and CD98 expression in pre-T cells and restore thymocyte differentiation. However, PDK1 L155E is insufficient for thymocyte proliferation. The role of PDK1 in thymus development thus extends beyond its ability to regulate PKB. In addition, PDK1 phosphorylation of AGC kinases such as S6K and RSK is also necessary for thymocyte development

    Neodymium elemental and isotopic composition of Oregon, USA margin sediments

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    The ability to reconstruct past ocean currents is essential for determining ocean circulation's role in global heat transport and climate change. Our understanding of the relationship between circulation and climate in the past allows us to predict the impact of future climate-driven circulation changes. One proposed tracer of past ocean circulation is the neodymium isotope composition (epsilon-Nd) of ancient water masses. However, ambiguities in what governs the epsilon-Nd distribution in the modern ocean hamper interpretations of this tracer. Here we present epsilon-Nd values for marine pore fluids, sediments, and the overlying water column for three sites in the North Pacific. We find that ocean bottom water epsilon-Nd (epsilon-NdBW) in the northeast Pacific lies between the value expected for the water mass (-3.3) and the measured epsilon-Nd of sediment pore fluid (epsilon-NdPW; -1.8). Moreover, epsilon-NdPW resembles the epsilon-Nd of the sediment. Combined, these findings are consistent with recent assessments that sediment pore fluids may be a major source of rare earth elements to the ocean and suggest that the benthic flux of Nd from pore fluids exerts the primary control over the deep ocean distribution of epsilon-Nd

    Elemental and neodymium isotopic composition of sediments from the Oregon, USA margin

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    Because ocean circulation impacts global heat transport, understanding the relationship between deep ocean circulation and climate is important for predicting the ocean's role in climate change. A common approach to reconstruct ocean circulation patterns employs the neodymium isotope compositions of authigenic phases recovered from marine sediments. In this approach, mild chemical extractions of these phases is thought to yield information regarding the epsilon-Nd of the bottom waters that are in contact with the underlying sediment package. However, recent pore fluid studies present evidence for neodymium cycling within the upper portions of the marine sediment package that drives a significant benthic flux of neodymium to the ocean. This internal sedimentary cycling has the potential to obfuscate any relationship between the neodymium signature recovered from the authigenic coating and the overlying neodymium signature of the seawater. For this manuscript, we present sedimentary leach results from three sites on the Oregon margin in the northeast Pacific Ocean. Our goal is to examine the potential mechanisms controlling the exchange of Nd between the sedimentary package and the overlying water column, as well as the relationship between the epsilon-Nd composition of authigenic sedimentary coatings and that of the pore fluid. In our comparison of the neodymium concentrations and isotope compositions from the total sediment, sediment leachates, and pore fluid we find that the leachable components account for about half of the total solid-phase Nd, therefore representing a significant reservoir of reactive Nd within the sediment package. Based on these and other data, we propose that sediment diagenesis determines the epsilon-Nd of the pore fluid, which in turn controls the epsilon-Nd of the bottom water. Consistent with this notion, despite having 1 to 2 orders of magnitude greater Nd concentration than the bottom water, the pore fluid is still <0.001% of the total Nd reservoir in the upper sediment column. Therefore, the pore fluid reservoir is too small to maintain a unique signature, and instead must be controlled by the larger reservoir of Nd in the reactive coatings. In addition, to achieve mass balance, we find it necessary to invoke a cryptic radiogenic (epsilon-Nd of +10) trace mineral source of neodymium within the upper sediment column at our sites. When present, this cryptic trace metal results in more radiogenic pore fluid

    Bottoms up : sedimentary control of the deep North Pacific Ocean's εNd signature

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    The ability to reconstruct past ocean currents is essential for determining ocean circulation’s role in global heat transport and climate change. Our understanding of the relationship between circulation and climate in the past allows us to predict the impact of future climate-driven circulation changes. One proposed tracer of past ocean circulation is the neodymium isotope composition (εNd) of ancient water masses. However, ambiguities in what governs the εNd distribution in the modern ocean hamper interpretations of this tracer. Here we present εNd values for marine pore fluids, sediments, and the overlying water column for three sites in the North Pacific. We find that ocean bottom water εNd (εNdBW) in the northeast Pacific lies between the value expected for the water mass (-3.3) and the measured εNd of sediment pore fluid (εNdPW;-1.8). Moreover, εNdPW resembles the εNd of the sediment. Combined, these findings are consistent with recent assessments that sediment pore fluids may be a major source of rare earth elements to the ocean and suggest that the benthic flux of Nd from pore fluids exerts the primary control over the deep ocean distribution of εNd.4 page(s
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