Abstract
G-protein-coupled receptors (GPCRs) are cell surface receptors and
are generally assumed to signal to second messengers such as cyclic
AMP (cAMP) exclusively from the plasma membrane. However, recent
studies indicate that GPCRs can continue signaling to cAMP after
internalization together with their agonists. Signaling from inside
the cell is persistent and appears to trigger specific downstream
effects. Here, we will review these recent data, which form the basis
for a novel concept of intracellular GPCR signaling and suggest new
and intriguing scenarios for the functions of GPCRs in the endocytic
compartment. We propose that current models of GPCR signaling should
be revised to accommodate the ability of receptors to change their
signaling properties depending on their subcellular localization.
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