title: Noncanonical intracrine action.
abstract: Over the past 3 decades it has become clear that a large number of extracellular signaling proteins/peptides also act in the intracellular space. These factors are termed intracrines and, although diverse in structure, they share a variety of functional features. In recent years, attention has increasingly turned to identifying the intracellular mechanisms of intracrine action and their implications for human disorders, such as cancer and cardiovascular disease. Perhaps not surprisingly, some intracrines have been shown to bind to and activate their cognate receptors located on intracellular membranes, such as the nuclear envelope. Here we discuss known intracrine actions and argue that mechanisms distinct from membrane receptor activation (that is, "noncanonical" actions) are often operative and physiologically relevant. These actions, we argue, expand our understanding of peptide signaling in important ways. Moreover, an appreciation of noncanonical intracrine functionality informs our understanding of the major effector protein of the renin-angiotensin system, angiotensin II, as well as other hormones operative in cardiovascular biology.
authors: Ochsner Clinic Foundation, New Orleans, LA, USA. rre@ochsner.org
authors: Richard N
authors: RN
authors: Re
authors: Julia L
authors: JL
authors: Cook
mesh_terms: D000804:Angiotensin II / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D042541:Intracellular Space / Q000502:physiology; D044162:Parathyroid Hormone-Related Protein / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D006023:Glycoproteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D044162:Parathyroid Hormone-Related Protein; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D005346:Fibroblast Growth Factors; C051795:teleocalcin