| Modification Notes |
Calcitonin (CT) is a circulating peptide hormone that is secreted from the thyroid and specifically binds to surface calcitonin receptors (CT-R) to regulate calcium homeostasis (1,2). These receptors represent a distinct family of seven transmembrane proteins, which include receptors for parathyroid hormone/parathyroid-related peptide, secretin and glucagon (2). CT-Rs induce intracellular signaling by coupling to multiple heterotrimeric G-proteins, where they then activate several signal transduction pathways involving adenylyl cyclase, phospholipase C and Map kinases (3). The gene encoding CT-R consists of numerous exons separated by larger introns, which are modified to produce multiple splice variants (4). These functionally unique isoforms display differential tissue distribution and preferentially associate with specific G-proteins to recruit distinct signaling intermediates (5). In osteoclasts and embryonic kidney cells, CT binding to the CT-R stimulates the Map kinases Erk1/2 and PKC activity through the phosphorylation of the adaptor proteins Shc and HEF1, and this induction occurs independently from PKA and adenylyl cyclase mediated signaling (6,7). |
