Substitution of the cysteine 438 residue in the cytoplasmic tail of the glucagon-like peptide-1 receptor alters signal transduction activity

Vázquez Pérez,  Patricia; Roncero Rincón, Isabel; Blázquez Fernández, Enrique; Álvarez García, Elvira

Substitution of the cysteine 438 residue in the cytoplasmic tail of the glucagon-like peptide-1 receptor alters signal transduction activity

Download

Substitution_of_the_cysteine_438_residue.pdf (451.41 KB)

Official URL

https://doi.org/10.1677/joe.1.06031

Publication date

2005

Authors

Vázquez Pérez, Patricia

Roncero Rincón, Isabel

Blázquez Fernández, Enrique

Álvarez García, Elvira

Editors

Bioscientifica

Publisher

BioScientifica

Citations

Exportar

URI

https://hdl.handle.net/20.500.14352/96187

Citation

Vázquez P, Roncero I, Blázquez E, Alvarez E. Substitution of the cysteine 438 residue in the cytoplasmic tail of the glucagon-like peptide-1 receptor alters signal transduction activity. J Endocrinol. 2005;185(1):35-44. doi:10.1677/joe.1.06031

Abstract

Several G-protein-coupled receptors contain cysteine residues in the C-terminal tail that may modulate receptor function. In this work we analysed the substitution of Cys438 by alanine in the glucagon-like peptide-1 (GLP-1) receptor (GLPR), which led to a threefold decrease in cAMP production, although endocytosis and cellular redistribution of GLP-1 receptor agonist-induced processes were unaffected. Additionally, cysteine residues in the C-terminal tail of several G-protein-coupled receptors were found to act as substrates for palmitoylation, which might modify the access of protein kinases to this region. His-tagged GLP-1 receptors incorporated 3H-palmitate. Nevertheless, substitution of Cys438 prevented the incorporation of palmitate. Accordingly, we also investigated the effect of substitution of the consensus sequence by protein kinase C (PKC) Ser431/432 in both wild-type and Ala438 GLP-1 receptors. Substitution of Ser431/432 by alanine did not modify the ability of wild-type receptors to stimulate adenylate cyclase or endocytosis and recycling processes. By contrast, the substitution of Ser431/432 by alanine in the receptor containing Ala438 increased the ability to stimulate adenylate cyclase. All types of receptors were mainly internalised through coated pits. Thus, cysteine 438 in the cytoplasmic tail of the GLP-1 receptor would regulate its interaction with G-proteins and the stimulation of adenylyl cyclase. Palmitoylation of this residue might control the access of PKC to Ser431/432.