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  • 1
    Electronic Resource
    Electronic Resource
    Serine residues 994 and 1023/25 are important for insulin receptor kinase inhibition by protein kinase C isoforms β2 and θ (2000)
    Springer
    Diabetologia 43 (2000), S. 443-449 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin receptor inhibition, tyrosine kinase activity, serine phosphorylation, protein kinase C.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Inhibition of the signalling function of the human insulin receptor (HIR) is one of the principle mechanisms which induce cellular insulin resistance. It is speculated that serine residues in the insulin receptor β-subunit are involved in receptor inhibition either as inhibitory phosphorylation sites or as part of receptor domains which bind inhibitory proteins or tyrosine phosphatases. As reported earlier we prepared 16 serine to alanine point mutations of the HIR and found that serine to alanine mutants HIR-994 and HIR-1023/25 showed increased tyrosine autophosphorylation when expressed in human embryonic kidney (HEK) 293 cells. In this study we examined whether these mutant receptors have a different susceptibility to inhibition by serine kinases or an altered tyrosine kinase activity.¶Methods. Tyrosine kinase assay and transfection studies.¶Results. In an in vitro kinase assay using IRS-1 as a substrate we could detect a higher intrinsic tyrosine kinase activity of both receptor constructs. Additionally, a higher capacity to phosphorylate the adapter protein Shc in intact cells was seen. To test the inhibition by serine kinases, the receptor constructs were expressed in HEK 293 cells together with IRS-1 and protein kinase C isoforms β2 and θ. Phorbol ester stimulation of these cells reduced wild-type receptor autophosphorylation to 58 % or 55 % of the insulin simulated state, respectively. This inhibitory effect was not observed with HIR-994 and HIR-1023/25, although all other tested HIR mutants showed similar inhibition induced by protein kinase C.¶Conclusion/interpretation. The data suggest that the HIR-domain which contains the serine residues 994 and 1023/25 is important for the inhibitory effect of protein kinase C isoforms β2 and θ on insulin receptor autophosphorylation. [Diabetologia (2000) 43: 443–449]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051327
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  • 2
    Electronic Resource
    Electronic Resource
    Untersuchung der Pentagastrinwirkung auf die Sekretion des Rattenmagens (1968)
    Springer
    Clinical and experimental medicine 148 (1968), S. 124-130 
    Details
    ISSN: 1591-9528
    Keywords: Stomach ; Pentagastrin ; Gastric fluid- and acid-secretion ; Secretion mechanism ; Magen ; Pentagastrin ; Saft- und Säuresekretion ; Sekretionsmechanismus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Eine dosisabhängige maximale Magensaftsekretion nach Pentagastrinstimulierung ist bei der Ratte mit einer Reizdosis von 40–50 μg zu erwarten. Bei kleineren Mengen bleibt das Saftvolumen unbeeinflußt, während die Säuresekretion einen mäßigen Anstieg verzeichnet. Bei höheren Dosen tritt ein Hemmeffekt auf unter Konstanthaltung des Sekretvolumens und Abfall der HCL-Ausschüttung. Bei unterschiedlicher Pentagastringabe läßt sich ein getrennter Sekretionsmechanismus für Wasser und Säure erkennen. Eine Erhöhung des Lösungsvolumens für Pentagastrin führt zu einer Verminderung der HCL-Gesamtmenge bei gleichzeitig reduziertem Magensaftvolumen.
    Notes: Summary The dose-dependent maximal secretion of gastric juice in the rat following pentagastrin stimulation is attainable at values of 25–50 μg. Lesser quantities are effective only upon hydrochloric acid production and not upon water secretion. Higher ones exercise a partially inhibiting action: the secretion volume remains constant, while the acid output decreases. The discordant action of different pentagastrin doses seems to bring evidence of distinct mechanisms for water and acid secretion. Dilution of the pentagastrin solution leads to a diminution of the acid while simultaneously reducing the volume of the gastric juice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02044244
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    Paper (German National Licenses)
    Fulltext
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