Objective
There have been several reports on the phosphorylation in vivo and in vitro of the insulin receptor on serine and/or threonine residues, in addition to the well characterized insulin stimulated autophosphorylation on tyrosines. The data supporting this conclusion were based on the existence in the wheatgerm agglutinin (WGA) eluates prepared from membrane extracts of a protein that migrated as the beta-subunit of the insulin receptor in sodium dodecyl sulphate - polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions which became phosphorylated on serine/threonine residues under diverse conditions. The coimmunoprecipitation of this protein with serum that contained antibodies against the insulin receptor gave further support to the identity of this protein as the beta-subunit of the receptor. In the preliminary stages of the work on the receptor from liver membranes of 6-week old rats evidence was obtained in favour of this interpretation. However, as the work proceeded, data suggested that the results should be reinterpreted considering the possible existence of:
different forms of the insulin receptor;
the presence in the WGA eluates of glycoproteins that could interfere with receptor phosphorylation;
the presence of other phosphorylatable proteins of apparent Mr similar to that of the beta-subunit.
Results indicate that there are indeed alterations in the properties of the insulin receptor in the livers of young obese rats. Furthermore, they show that caution should be taken on the presence of 2 peaks and other phosphorylatable proteins when comparing the hepatic insulin receptors from different physiopathological conditions.
The aim of the present project is to unravel the implications of the serine/threonine phosphorylation of the hepatic insulin receptor for signal transduction and receptor recycling. Initially the
phosphorylation state and the tyrosine kinase activity of the receptor will be characterized in hyper- and hypo-insulinemic adult and in fetal rats. To this purpose, the effect of various protein kinases and protein phosphatases will be investigated on isolated insulin receptors. Subsequent experiments with the use of cultured
hepatocytes and hepatoma cells are designed to define the role of the different protein kinases in receptor phosphorylation 'in vivo'.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology environmental engineering waste management waste treatment processes recycling
- natural sciences chemical sciences inorganic chemistry alkali metals
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences chemical sciences electrochemistry electrophoresis
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Coordinator
08193 BELLATERRA
Spain
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