title: Negative regulators of integrin activity.
abstract: Integrins are heterodimeric transmembrane adhesion receptors composed of α- and β-subunits. They are ubiquitously expressed and have key roles in a number of important biological processes, such as development, maintenance of tissue homeostasis and immunological responses. The activity of integrins, which indicates their affinity towards their ligands, is tightly regulated such that signals inside the cell cruicially regulate the switching between active and inactive states. An impaired ability to activate integrins is associated with many human diseases, including bleeding disorders and immune deficiencies, whereas inappropriate integrin activation has been linked to inflammatory disorders and cancer. In recent years, the molecular details of integrin 'inside-out' activation have been actively investigated. Binding of cytoplasmic proteins, such as talins and kindlins, to the cytoplasmic tail of β-integrins is widely accepted as being the crucial step in integrin activation. By contrast, much less is known with regard to the counteracting mechanism involved in switching integrins into an inactive conformation. In this Commentary, we aim to discuss the known mechanisms of integrin inactivation and the molecules involved.
authors: Centre for Biotechnology, University of Turku, Turku, Finland.
authors: Jeroen
authors: J
authors: Pouwels
authors: Jonna
authors: J
authors: Nevo
authors: Teijo
authors: T
authors: Pellinen
authors: Jari
authors: J
authors: Ylänne
authors: Johanna
authors: J
authors: Ivaska
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism; D039641:Integrin beta Chains / Q000378:metabolism; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D015398:Signal Transduction
chemical_list: D039001:Integrin alpha Chains; D039641:Integrin beta Chains; D016023:Integrins