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Studies on the pathway and significance of the receptor mediated internalization of insulin and epidermal growth factor in rat liver parenchyma

The pathway of internalization of insulin and asialoglycoprotein into rat liver parenchymal cells was through the same endosomal components. At no time was either ligand associated with the biosynthetic Golgi apparatus. Rat liver Golgi fractions were found to be contaminated by endosomes, hence their redesignation as Golgi-endosome fractions (GE). / Proton translocation activity of different GE fractions showed a gradient of progressively decreasing activity which correlated with increasing time, of ligand accumulation therein. Based on the distinctive kinetics of proton translocation activity and ligand accumulation the endosomal components of the Golgi intermediate and light fractions, which fractionate coincidently on percoll gradient centrifugation, have been considered to be distinct components of the endocytic apparatus. / The activity of the EGF receptor kinase has been assessed in plasmalemmal and GE fractions isolated from untreated animals as well as those injected with EGF in vivo. In untreated animals receptor kinase activity was readily detected in plasmalemmal fractions, but was latent in GE fractions, suggesting an intraluminal orientation of the EGF binding region of the receptor in endosomes. Consequent to the administration of EGF in vivo a majority of the receptor kinase translocated from plasmalemma to endosomes. Receptor kinase activity remaining on the plasmalemma was activated. Endosomally located receptor kinase activity was no longer latent following EGF administration, was maximally stimulated with respect to autophosphorylation activity and at later times following internalization, may become activated. These data are consistent with a role for both plasmalemmal and endosomally located EGF receptor kinase in transmembrane signalling.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.75441
Date January 1987
CreatorsKay, Denis G.
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageDoctor of Philosophy (Department of Anatomy.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 000425561, proquestno: AAINL44353, Theses scanned by UMI/ProQuest.

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