| Popis: |
Endocrine FGFs (FGF19, FGF21, and FGF23) require Klotho proteins to bind to and activate FGF receptor (FGFR) tyrosine kinases. A bone-derived hormone FGF23 acts on renal tubules and parathyroid glands that express α-Klotho to maintain phosphate and calcium homeostasis. FGF19 is secreted from intestinal epithelium upon feeding and acts on hepatocytes that express β-Klotho and FGFR4 to induce metabolic responses to feeding. Conversely, FGF21 is secreted upon fasting from hepatocytes and acts on adipocytes and neurons in the brain stem that express β-Klotho and FGFR1c to induce lipolysis and sympathetic activation. Endocrine FGFs exert these effects in their target tissues mainly through activating the canonical FGF signaling pathway culminating in activation of extracellular signal–regulated kinase. The FGF-Klotho endocrine system is unique to vertebrates that might have evolved in the necessity to maintain the bone made of calcium phosphate and to survive famine periods. |
