Modulation of signalling initiated by phosphoinositidase-C-linked receptors

An extensive group of cell surface receptors are coupled to phosphoinositidase C and thus to the production of the intracellular second messengers inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. While the mechanisms and consequences of phosphoinositidase C activation have been the target of intensive study for over a decade, information is scarce regarding the regulatory processes that modulate this system during receptor stimulation. This situation, however, is now beginning to change. Recent data indicate (a) that Ca2+, mobilized concurrently with activation of phosphoinositidase-C-linked receptors, is a feedback activator and amplifier of phosphoinositide hydrolysis, (b) that rapid desensitization, possibly associated with receptor phosphorylation, regulates phosphoinositidase-C-linked receptors, (c) that receptor internalization can mediate desensitization at later times and (d) that signalling can be regulated at additional sites downstream of phosphoinositidase C. These diverse regulatory events provide the means by which the breakdown of phosphoinositides and cellular responsiveness to their products are controlled during cell stimulation.