| 1. |
- Larsson, Mårten, et al.
(författare)
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Selective interaction of megalin with postsynaptic density-95 (PSD-95)-like membrane-associated guanylate kinase (MAGUK) proteins
- 2003
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Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 373:2, s. 381-391
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Tidskriftsartikel (refereegranskat)abstract
- Megalin is an integral membrane receptor belonging to the low-density lipoprotein receptor family. In addition to its role as an endocytotic receptor, megalin has also been proposed to have signalling functions. Using interaction cloning in yeast, we identified the membrane-associated guanylate kinase family member postsynaptic density-95 (PSD-95) as an interaction partner for megalin. PSD-95 and a truncated version of megalin were co-immunoprecipitated from HEK-293 cell lysates overexpressing the two proteins, which confirmed the interaction. The two proteins were found to be co-localized in these cells by confocal microscopy. Immunocytochemical studies showed that cells in the parathyroid, proximal tubuli of the kidney and placenta express both megalin and PSD-95. We found that the interaction between the two proteins is mediated by the binding of the C-terminus of megalin, which has a type I PSD-95/ Drosophila discs-large/zona occludens 1 (PDZ)-binding motif, to the PDZ2 domain of PSD-95. The PSD-95-like membrane-associated guanylate kinase ('MAGUK') family contains three additional members: PSD-93, synapse-associated protein 97 (SAP97) and SAP102. We detected these proteins, apart from SAP102, in parathyroid chief cells, a cell type having a marked expression of megalin. The PDZ2 domains of PSD-93 and SAP102 were also shown to interact with megalin, whereas no interaction was detected for SAP97. The SAP97 PDZ2 domain differed at four positions from the other members of the PSD-95 subfamily. One of these residues was Thr(389), located in the alphaB-helix and part of the hydrophobic pocket of the PDZ2 domain. Surface plasmon resonance experiments revealed that mutation of SAP97 Thr(389) to alanine, as with the other PSD-95-like membrane-associated guanylate kinases, induced binding to megalin.
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| 2. |
- Hagbeg, Bengt, et al.
(författare)
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Odd MECP2-mutated Rett variant : long-term follow-up profile to age 25
- 2003
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Ingår i: European journal of paediatric neurology. - : Elsevier BV. - 1090-3798 .- 1532-2130. ; 7:6, s. 417-421
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Tidskriftsartikel (refereegranskat)abstract
- A 25-year-old MECP2-mutated female with odd developmental and dyspraxic/ataxic features, followed up through two decades, is reported. She does not fit either the classical Rett syndrome or the criteria required for any Rett variant phenotypes so far described. Nevertheless, she belongs clinically to the latter group. This case deserves attention in order, among other things, to provide important clues to better understand the puzzling battery of neuroimpairments and behavioural abnormalities met in classical Rett phenotypes and Rett variants defined thus far.
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| 3. |
- Irobi, Edward, et al.
(författare)
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Structural basis of actin sequestration by thymosin β4 : implications for WH2 proteins
- 2004
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Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 23:18, s. 3599-608
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Tidskriftsartikel (refereegranskat)abstract
- The WH2 (Wiscott-Aldridge syndrome protein homology domain 2) repeat is an actin interacting motif found in monomer sequestering and filament assembly proteins. We have stabilized the prototypical WH2 family member, thymosin-beta4 (Tbeta4), with respect to actin, by creating a hybrid between gelsolin domain 1 and the C-terminal half of Tbeta4 (G1-Tbeta4). This hybrid protein sequesters actin monomers, severs actin filaments and acts as a leaky barbed end cap. Here, we present the structure of the G1-Tbeta4:actin complex at 2 A resolution. The structure reveals that Tbeta4 sequesters by capping both ends of the actin monomer, and that exchange of actin between Tbeta4 and profilin is mediated by a minor overlap in binding sites. The structure implies that multiple WH2 motif-containing proteins will associate longitudinally with actin filaments. Finally, we discuss the role of the WH2 motif in arp2/3 activation.
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| 4. |
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| 5. |
- Jonasson, Jan-Erik, et al.
(författare)
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Temperatursprickor i betongkonstruktioner : handbok med diagram för sprickriskbedömning inklusive åtgärder för några vanliga typfall. Del D och E
- 2001
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Föreliggande handbok är framtagen i ett SBUF-projekt med Kjell Wallin, Peab som projektledare. Projektet har genomförts i nära samarbete mellan Peab Sverige AB och Luleå tekniska universitet. Arbetet har inneburit att ett stort antal datorberäkningar har genomförts, och de redovisas i diagramform i denna handbok. Resultaten avses att användas att fylla i en blankett i ett Excel-ark. Syftet är att för typfallet vägg-på-platta ska handboken ge underlag för sprickriskbedömning och i förekommande fall ange vilka typåtgärder som ska sättas in. Avsikten är därvid att man inte ska behöva göra några externa beräkningar, men användaren har full frihet att själv ta fram temperaturen eller tvångssituationen på godtyckligt annat sätt. Handboksmetodiken avser en fortsättning på det som i Bronormen (Bro 94, bilaga 9-5) kallas metod 2, och den redovisade kompletteringen innefattar främst att erforderliga åtgärder (kylning och/eller värmning) för det valda typfallet inkluderas.
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| 6. |
- Larsson, Mårten
(författare)
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Linear logarithmic model for concrete creep III
- 2002
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In this report the results from an evaluation of a new basic creep model and prediction formulas, primarily aimed for young concrete, are summarised. The formulation is based on piece-wise linear curves in logarithm of time and therefore denoted the Linear Logarithmic Model, LLM, which forms a base for the prediction formulas that with a minimum of material testing still can predict a reliable creep development.
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| 10. |
- Sakwe, Amos M., et al.
(författare)
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Biosynthesis and secretion of parathyroid hormone are sensitive to proteasome inhibitors in dispersed bovine parathyroid cells
- 2002
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 277:20, s. 17687-17695
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Tidskriftsartikel (refereegranskat)abstract
- Preproparathyroid hormone (prepro-PTH) is one of the proteins abundantly synthesized by parathyroid chief cells; yet under normal growth conditions, little or no prepro-PTH can be detected in these cells. Although this may be attributed to effective cotranslational translocation and proteolytic processing, proteasome-mediated degradation of PTH precursors may be important in the regulation of the levels of these precursors and hence PTH secretion. The effects of N-acetyl-Leu-Leu-norleucinal, N-acetyl-Leu-Leu-methional, carbobenzoxy-Leu-Leu-leucinal (MG132), benzyloxycarbonyl-Ile-Glu(t-butyl)-Ala-leucinal (proteasome inhibitor I), and lactacystin on the biosynthesis and secretion of PTH were examined in dispersed bovine parathyroid cells. We demonstrate that treatment of these cells with proteasome inhibitors caused the accumulation of prepro-PTH and pro-PTH. Compared with mock-treated cells, the processing of pro-PTH to PTH was delayed, and the secretion of intact PTH decreased in proteasome inhibitor-treated cells. Relieving the inhibition of the proteasome by chasing MG132-treated cells in medium without the inhibitor led to the rapid disappearance of the accumulated prepro-PTH, and the rate of PTH secretion was restored to levels comparable to those in mock-treated cells. Furthermore, overexpression of the Hsp70 family of molecular chaperones was observed in proteasome inhibitor-treated cells, and we show that PTH/PTH precursors interact with these molecular chaperones. These data suggest the involvement of parathyroid cell proteasomes in the quality control of PTH biosynthesis.
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| 11. |
- Sakwe, Amos M., et al.
(författare)
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Involvement of protein kinase C-alpha and -epsilon in extracellular Ca(2+) signalling mediated by the calcium sensing receptor
- 2004
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 297:2, s. 560-573
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Tidskriftsartikel (refereegranskat)abstract
- The sensing of extracellular Ca(2+) concentration ([Ca(2+)](o)) and modulation of cellular processes associated with acute or sustained changes in [Ca(2+)](o) are cell-type specific and mediated by the calcium sensing receptor (CaR). [Ca(2+)](o) signalling requires protein kinase C (PKC), but the identity and role of PKC isoforms in CaR-mediated responses remain unclear. Here we show that high [Ca(2+)](o) activated PKC-alpha and PKC- in parathyroid cells and in human embryonic kidney (HEK293) cells overexpressing the CaR (HEK-CaR) and that this response correlated with the CaR-dependent activation of mitogen-activated protein kinases ERK1/2. Activation of ERK1/2 by acute high [Ca(2+)](o) required influx of Ca(2+)through Ni(2+)-sensitive Ca(2+)channels and phosphatidylinositol-dependent phospholipase C-beta activity. Inhibition of PKC by co-expression of dominant-negative (DN) mutants of PKC-alpha or - with the CaR attenuated sustained ERK1/2 activation. Overexpression of a PKC phosphorylation site (T888A) mutant CaR in HEK293 cells showed that this site was important for ERK1/2 activation at high [Ca(2+)](o). Activation of ERK1/2 by high [Ca(2+)](o) was not necessary for the [Ca(2+)](o)-regulated secretion of parathyroid hormone (PTH) in dispersed bovine parathyroid cells. These data suggest that the CaR-mediated [Ca(2+)](o) signal leading to regulated PTH secretion that requires diacylglycerol-responsive PKC isoforms is not mediated via the ERK pathway.
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