Question

While comparing the amino acid sequences of many different GPCRs, you notice the presence of conserved serine and threonine amino acids on the same cytosolic region of each receptor. You change the DNA sequence so that all of the conserved serine and threonine amino acids in the cytosolic region are converted to glutamic acid. Which of the following effects would you most likely see when cells expressing this modified GPCR are exposed to ligand compared to your control cells that do not express the modified GPCR?

A	The modified GPCR would rapidly undergo endocytosis and not signal.

B	Cells expressing the modified GPCR will display a sustained response compared to the control cells.

C	The modified GPCR will be recycled to the cell surface more rapidly than the modified GPCR.

D	Cells expressing the modified GPCR will display a reduced response more quickly than control cells.

Answer 1

Option A is the correct answer. GPCR signaling occurs via phosphorylation of cytosolic serine and threonine residues localized within either the third intracellular loop or carboxyl-terminal tail domains by G protein coupled-receptors kinases (GRKs).  Substitution of all of the serine and threonine residues with any amino acids including glutamic acid within either the carboxyl-terminal tail or the third intracellular loop abolishes GRK-mediated phosphorylation of these receptors. Thus, modified GPCR will undergo endocytosis and degrade by ubiquitin proteasome pathway.