Phosphate as a Signaling Molecule

Kittrawee Kritmetapak, Rajiv Kumar

Research output: Contribution to journalReview article

1 Scopus citations

Abstract

Phosphorus plays a vital role in diverse biological processes including intracellular signaling, membrane integrity, and skeletal biomineralization; therefore, the regulation of phosphorus homeostasis is essential to the well-being of the organism. Cells and whole organisms respond to changes in inorganic phosphorus (Pi) concentrations in their environment by adjusting Pi uptake and altering biochemical processes in cells (local effects) and distant organs (endocrine effects). Unicellular organisms, such as bacteria and yeast, express specific Pi-binding proteins on the plasma membrane that respond to changes in ambient Pi availability and transduce intracellular signals that regulate the expression of genes involved in cellular Pi uptake. Multicellular organisms, including humans, respond at a cellular level to adapt to changes in extracellular Pi concentrations and also have endocrine pathways which integrate signals from various organs (e.g., intestine, kidneys, parathyroid glands, bone) to regulate serum Pi concentrations and whole-body phosphorus balance. In mammals, alterations in the concentrations of extracellular Pi modulate type III sodium–phosphate cotransporter activity on the plasma membrane, and trigger changes in cellular function. In addition, elevated extracellular Pi induces activation of fibroblast growth factor receptor, Raf/mitogen-activated protein kinase/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) and Akt pathways, which modulate gene expression in various mammalian cell types. Excessive Pi exposure, especially in patients with chronic kidney disease, leads to endothelial dysfunction, accelerated vascular calcification, and impaired insulin secretion.

Original languageEnglish (US)
JournalCalcified Tissue International
DOIs
StateAccepted/In press - Jan 1 2019

Keywords

  • Chronic kidney disease
  • Phosphate
  • Phosphorus
  • Signaling

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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