Project: Research project

Project Details


The aim of the project is a better understanding of the role of protein
phosphorylation in the mechanisms of action of hormones such as insulin,
glucagon and catecholamines. The initial target of hormonal control to be
studied is glycogen metabolism, and in particular, the multiply
phosphorylated enzyme, glycogen synthase, in liver and muscle. What is the
detailed relationship between covalent phosphorylation and glycogen
synthase activity? Which phosphorylation sites are linked to the actions
of different hormones? What are the different protein kinases and
phosphatases involved? Can mechanisms of regulating the converting enzymes
be identified? How does the potential regulation in liver and muscle
differ, and can differences be related to the distinct roles of glycogen in
these two tissues? Experimental approaches will combine the study of
isolated enzymes with investigations of intact muscle and isolated
hepatocytes. A long term objective is to improve knowledge of the
diversity of protein kinases present in cells and of their potential roles
in different cellular processes. In this way, it may be possible to build
a wider and more coordinated view of the regulatory role of protein
phosphorylation, and hopefully link this with the action of hormones and
other extracellular agents. The thrust of the whole program is to analyze
hormonal and cellular controls at a biochemical level. Of course, we
believe that advancements in the knowledge of the mechanisms of action of
insulin, glucagon and catecholamines can have important implications for
pathological situations, notably in the case of impaired insulin function,
for insulin-dependent and insulin-independent diabetes.
Effective start/end date7/1/826/30/87


  • National Institutes of Health


  • Medicine(all)


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