CRF signaling is mediated by CRF receptors, subtype 1 (CRF1) and/or subtype 2 (CRF2), cloned from two distinct genes (14,81). Both receptors belong to the class of seven-trans-membrane receptors that signal by coupling to Gs proteins (82,83). One important feature of CRF receptor subtypes is their distinct affinity for mammalian CRF family ligands including CRF and urocortin 1 (also known as urocortin), and the recently discovered urocortin 2 and urocortin 3 (83,84). CRF displays 10- to 40-fold higher affinity for the CRF1 than CRF2 receptor. Urocortin 1 binds with equal affinity to CRF1 and CRF2 receptors and, compared with CRF, displays approximately 100-fold higher affinity to CRF2 and roughly a 6-fold higher affinity for CRF1 (85-87). Both urocortin 2 and urocortin 3 exhibit high selectivity for the CRF2 receptor (85,86). These binding characteristics have positioned CRF and urocortin 1 as the preferential endogenous ligands for CRF1 receptors, whereas urocortins; 2 and 3 are likely the natural ligands for CRF2.
Was this article helpful?