title: The serum- & glucocorticoid-inducible kinase in the regulation of platelet function.
abstract: The serum- and glucocorticoid-inducible kinase 1 (SGK1) is expressed in megakaryocytes and circulating platelets. In megakaryocytes, SGK1 activates transcription factor nuclear factor kappa-B (NF-κB), which in turn stimulates expression of Orai1, a Ca(2+) channel protein accomplishing store-operated Ca(2+) enrty (SOCE). SGK1 enhances SOCE and several Ca(2+) -sensitive platelet functions, including degranulation, integrin αII b β3 activation, phosphatidylserine exposure, aggregation and thrombus formation. As shown in other cell types, stimulators of SGK1 expression include ischaemia, oxidative stress, hyperglycaemia, advanced glycation end products (AGEs) and a variety of hormones such as glucocorticoids, mineralocorticoids, transforming growth factor beta (TGFβ), interleukin 6 (IL-6), platelet-derived growth factor (PDGF), thrombin and endothelin. Thus, SGK1-sensitive Ca(2+) signalling may contribute to altered platelet function in several clinical conditions including inflammation, metabolic syndrome, diabetes mellitus and chronic renal failure. Nevertheless, further studies are needed defining the contribution of altered SGK1 expression and activity to physiology and pathophysiology of platelets.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Lang
authors.forename: M
authors.initials: M
authors.lastname: Gawaz
authors.forename: O
authors.initials: O
authors.lastname: Borst
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D005938:Glucocorticoids; D017346:Protein Serine-Threonine Kinases; C444640:serum-inducible kinase
keywords: Ca2+; Orai1; SGK1; metabolic syndrome; platelets; thrombus formation