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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
    In vitro-Verfahren zur autoradiographischen Untersuchung der Zellerneuerung der menschlichen Magenschleimhaut am Biopsiematerial (1972)
    Springer
    Journal of molecular medicine 50 (1972), S. 56-57 
    Details
    ISSN: 1432-1440
    Keywords: In-vitro-autoradiography ; stomach biopsies ; cell regeneration ; In vitro-Autoradiographie ; Magenschleimhautbiopsie ; Zellregeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Zur autoradiographischen Untersuchung der Zellerneuerung in der Magenschleimhaut des Menschen wurde ein früher entwickeltes in vitro-Verfahren am Biopsiematerial angewendet. Bei gleichbleibenden Versuchsbedingungen und einem Gewebsdurchmesser bis ca. 1000 µ wurden Autoradiogramme erhalten, die geeignet erscheinen, die Magenmucosa unter verschiedenen pathologischen Bedingungen zu untersuchen.
    Notes: Summary Autoradiography with bioptic specimens of human gastric mucosa. A previously tested in-vitro method was applied for an autoradiographical study of cell proliferation of the mucosa of the human stomach in biopsies under standardized conditions. From specimens of about 1000 µ in diameter autoradiographs can be obtained which show the characteristic labelling of cells in the zones of cell regeneration and permit the investigation of the normal and pathological mucosa of the human stomach.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01487778
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    Paper (German National Licenses)
    Fulltext
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