Study of human tsh-receptor activating mutations

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Project objective

Somatic and germinal mutations of the human Thyrotropin-receptor have been found in cases of thyroid toxic adenomas and thyroid toxic hyperplasia respectively, more frequently than was expected, and in different regions of the receptor. Functional characterization of these mutations shows that they lead to a constitutive activation of the TSH-receptor producing thyroid cell proliferation and hyperfunction. Wild- type receptor also apparently displays some constitutive activity in contrast to other G-protein coupled receptors. New mutations will be searched and more precisely characterized for ligand affinity, and coupling efficiency through transfection experiments. Equivalent mutations will be produced in related receptors (LH and FSH receptors) and chimeric receptors to study the functional importance of the mutated residues in terms of constitutive activity and signal transduction. Mapping of functional regions should be obtained with a better knowledge of transduction mechanisms through G-protein coupled receptors

Original text from CORDIS.

Participants

• UNIVERSITE LIBRE DE BRUXELLES · BRUXELLESCoordinatorBelgium
• Not availableCity levelFrance

Links

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