title: Insights into mechanisms of corticotropin-releasing hormone receptor signal transduction.
abstract: During evolution, mammals have developed remarkably similar molecular mechanisms to respond to external challenges and maintain survival. Critical regulators of these mechanisms are the family of 'stress'-peptides that consists of the corticotropin-releasing hormone (CRH) and urocortins (Ucns). These neuropeptides 'fine-tune' integration of an intricate series of physiological responses involving the autonomic, endocrine, immune, cardiovascular and reproductive systems, which induce a spectrum of behavioural and homeostatic changes. CRH and Ucns exert their actions by activating two types of CRH receptors (CRH-R), CRH-R1 and CRH-R2, which belong to the class-B1 family of GPCRs. The CRH-Rs exhibit signalling promiscuity facilitated by their ability to couple to multiple G-proteins and regulate diverse intracellular networks that involve intracellular effectors such as cAMP and an array of PKs in an agonist and tissue-specific manner, a property that allows them to exert unique roles in the integration of homeostatic mechanisms. We only now begin to unravel the plethora of CRH-R biological actions and the transcriptional and post-translational mechanisms such as alternative mRNA splicing or phosphorylation-mediated desensitization developed to tightly control CRH-Rs biological activity and regulate their physiological actions. This review summarizes the current understanding of CRH-R signalling complexity and regulatory mechanisms that underpin cellular responses to CRH and Ucns.
authors: University of Warwick, Coventry, UK. d.grammatopoulos@warwick.ac.uk
authors: Dimitris K
authors: DK
authors: Grammatopoulos
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D054832:Urocortins / Q000378:metabolism*; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP