Lysophosphatidic acid signaling: How a small lipid does big things

Lysophosphatidic acid (LPA) promotes growth, differentiation, survival and motility in many different cell types. LPA has therefore been suggested to play a central role in a broad range of physiological and pathophysiological processes, including vascular and neuronal function and cancer. Three closely related G-protein-coupled cell-surface receptors mediate some of these effects, but assigning specific functions to particular receptor subtypes has been challenging and several lines of evidence indicate that other LPA signaling mechanisms might exist. Although the signaling actions of LPA have been studied widely, much less is known about how LPA is generated and released into the extracellular space, and how its signaling actions are terminated. Newly identified enzymes that generate and inactivate LPA have novel roles in cancer progression and early development, and a recent study indicates that LPA might regulate nuclear gene transcription directly. These findings provide novel insights into mechanisms involved in the synthesis, actions and inactivation of LPA, and the proteins involved provide new targets that can be exploited to manipulate LPA signaling at both cellular and organismal levels.