Phosphate as a sensor and signaling molecule

In prokaryotes and eukaryotes inorganic phosphate plays a vital role in many cellular and biological processes. Maintenance of proper phosphate homeostasis is therefore essential and any deviation from that state can lead to several acute and chronic disease states. In order to maintain physiological levels, a tightly regulated phosphate sensing and signaling mechanism needs to exist. The earliest and best characterized mechanisms of phosphate sensing and signaling have been described in yeast and bacteria involving the Pho regulon. The Pho regulon has been shown to function in a coordinated fashion in order to meet the cellular needs of the organism. Studies have also shown that the protein kinase A (PKA) signaling pathway is involved in phosphate metabolism. In eukaryotes, due to the complexity of the regulatory mechanisms and involvement of several key regulators of phosphate secreted from different organs, it has been difficult to identify the phosphate sensor. Nonetheless the crosstalk between organs in response to phosphate provides strong evidence to support the existence of such a mechanism. This review will focus on this evidence and highlight the parallels tha exist with the Pho regulon. We will focus on the kidney-arathyroid, kidney-intestinal, parathyroid-intestinal, kidney-bone, and finally the parathyroid-bone axes.