DESENSITIZATION OF CELL SIGNALING MEDIATED BY PHOSPHOINOSITIDASE-C

The waning of responses to cell-surface receptor activation during per sistent stimulation with agonists (desensitization) is a feature commo n to many forms of transmembrane signalling. However, information is s carce regarding the regulatory processes that modulate the extensive g roup of receptors linked via phosphoinositidase C to the production of inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. This situation i s now beginning to change. Recent data indicate (1) that very rapid de sensitization, possibly associated with receptor phosphorylation, regu lates receptors linked to phosphoinositidase C, (2) that different rec eptors are desensitized to varying extents, (3) that receptor internal ization can mediate desensitization at later times and (4) that signal ling can be regulated at additional sites downstream of phosphoinositi dase C. As Richard Wojcikiewicz and colleagues discuss here, these div erse regulatory events provide the means by which the breakdown of pho sphoinositides and cellular responsiveness to their products are contr olled during cell stimulation.