Regulation of bifunctional proteins in cells: Lessons from the phospholipase C beta/G protein pathway

Some proteins can serve multiple functions depending on different cellular conditions. An example of a bifunctional protein is inositide-specific mammalian phospholipase C beta (PLC beta). PLC beta is activated by G proteins in response to hormones and neurotransmitters to increase intracellular calcium. Recently, alternate cellular function(s) of PLC beta have become uncovered. However, the conditions that allow these different functions to be operative are unclear. Like many mammalian proteins, PLC beta has a conserved catalytic core along with several regulatory domains. These domains modulate the intensity and duration of calcium signals in response to external sensory information, and allow this enzyme to inhibit protein translation in a noncatalytic manner. In this review, we first describe PLC beta's cellular functions and regulation of the switching between these functions, and then discuss the thermodynamic considerations that offer insight into how cells manage multiple and competitive associations allowing them to rapidly shift between functional states.