If one were to judge by the sheer number of receptors to which they are coupled, the phospholipids and their metabolites would be arguably the most important of all second messengers (Figure 1). What is so special about phospholipids and phospholipid signaling proteins? The phosphoinositides and other signal-transducing phospholipids are compartmentalized in distinct pools in the various membranes of the cell, separated by aqueous phase barriers. Most of the proteins involved are amphitropic, meaning they can exist as either membrane or soluble proteins. Reversible translocation between the cytosol and different cell membranes is a central feature of their cell biology. The activities of the proteins feature the full range of complexities of interfacial enzymology; their evolution reflects the unique requirements of life.
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