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10.1182/blood-2011-06-359976 http://scihub22266oqcxt.onion/10.1182/blood-2011-06-359976 22031864!ä!22031864 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Blood 2012 ; 119 (1): 251-61 Nephropedia Template TP {{tp|p=22031864|t=2012. The serum- and glucocorticoid-inducible kinase 1 (SGK1) influences platelet calcium signaling and function by regulation of Orai1 expression in megakaryocytes |pdf=|usr=}}{{22031864}} gab.com Text The serum- and glucocorticoid-inducible kinase 1 (SGK1) influences platelet calcium signaling and function by regulation of Orai1 expression in megakaryocytes JO: Blood http://www.kidney.de/pget.php?&tw=1&pmid=22031864 #FOAvip Platelets are activated on increase of cytosolic Ca2+ activity ([Ca2+](i)), accomplished by store-operated Ca2+ entry (SOCE) involving the pore-forming ion channel subunit Orai1. Here, we show, for the first time, that the serum- and glucocorticoid-inducible kinase 1 (SGK1) is expressed in platelets and megakaryocytes. SOCE and agonist-induced [Ca2+](i) increase are significantly blunted in platelets from SGK1 knockout mice (sgk1(-/-)). Similarly, Ca2+ -dependent degranulation, integrin alpha(IIb)beta3 activation, phosphatidylserine exposure, aggregation, and in vitro thrombus formation were significantly impaired in sgk1(-/-) platelets, whereas tail bleeding time was not significantly enhanced. Platelet and megakaryocyte Orai1 transcript levels and membrane protein abundance were significantly reduced in sgk1(-/-) mice. In human megakaryoblastic cells (MEG-01), transfection with constitutively active (S422D)SGK1 but not with inactive (K127N)SGK1 significantly enhanced Orai1 expression and SOCE, while effects reversed by the SGK1 inhibitor GSK650394 (1muM). Transfection of MEG-01 cells with (S422D)SGK1 significantly increased phosphorylation of IkappaB kinase alpha/beta and IkappaBalpha resulting in nuclear translocation of NF-kappaB subunit p65. Treatment of (S422D)SGK1-transfected MEG-01 cells with the IkappaB kinase inhibitor BMS-345541 (10muM) abolished SGK1-induced increase of Orai1 expression and SOCE. The present observations unravel SGK1 as novel regulator of platelet function, effective at least in part by NF-kappaB-dependent transcriptional up-regulation of Orai1 in megakaryocytes and increasing platelet SOCE. Twit Text FOAVip The serum- and glucocorticoid-inducible kinase 1 (SGK1) influences platelet calcium signaling and function by regulation of Orai1 expression in megakaryocytes ????Blood http://www.kidney.de/pget.php?&tw=1&pmid=22031864 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=22031864 #FOAvip English Wikipedia <ref>{{Cite pmid|22031864}}</ref> The serum- and glucocorticoid-inducible kinase 1 (SGK1) influences platelet calcium signaling and function by regulation of Orai1 expression in megakaryocytes #MMPMID22031864 Borst O; Schmidt EM; Munzer P; Schonberger T; Towhid ST; Elvers M; Leibrock C; Schmid E; Eylenstein A; Kuhl D; May AE; Gawaz M; Lang F Blood 2012[Jan]; 119 (1): 251-61 PMID22031864show ga Platelets are activated on increase of cytosolic Ca2+ activity ([Ca2+](i)), accomplished by store-operated Ca2+ entry (SOCE) involving the pore-forming ion channel subunit Orai1. Here, we show, for the first time, that the serum- and glucocorticoid-inducible kinase 1 (SGK1) is expressed in platelets and megakaryocytes. SOCE and agonist-induced [Ca2+](i) increase are significantly blunted in platelets from SGK1 knockout mice (sgk1(-/-)). Similarly, Ca2+ -dependent degranulation, integrin alpha(IIb)beta3 activation, phosphatidylserine exposure, aggregation, and in vitro thrombus formation were significantly impaired in sgk1(-/-) platelets, whereas tail bleeding time was not significantly enhanced. Platelet and megakaryocyte Orai1 transcript levels and membrane protein abundance were significantly reduced in sgk1(-/-) mice. In human megakaryoblastic cells (MEG-01), transfection with constitutively active (S422D)SGK1 but not with inactive (K127N)SGK1 significantly enhanced Orai1 expression and SOCE, while effects reversed by the SGK1 inhibitor GSK650394 (1muM). Transfection of MEG-01 cells with (S422D)SGK1 significantly increased phosphorylation of IkappaB kinase alpha/beta and IkappaBalpha resulting in nuclear translocation of NF-kappaB subunit p65. Treatment of (S422D)SGK1-transfected MEG-01 cells with the IkappaB kinase inhibitor BMS-345541 (10muM) abolished SGK1-induced increase of Orai1 expression and SOCE. The present observations unravel SGK1 as novel regulator of platelet function, effective at least in part by NF-kappaB-dependent transcriptional up-regulation of Orai1 in megakaryocytes and increasing platelet SOCE. |*Calcium Signaling[MESH] |Animals[MESH] |Bleeding Time[MESH] |Blood Platelets/*metabolism[MESH] |Blotting, Western[MESH] |Calcium Channels/genetics/*metabolism[MESH] |Calcium/*metabolism[MESH] |Cells, Cultured[MESH] |Female[MESH] |Flow Cytometry[MESH] |Fluorescent Antibody Technique[MESH] |Humans[MESH] |Immediate-Early Proteins/*physiology[MESH] |Immunoenzyme Techniques[MESH] |Leukemia, Megakaryoblastic, Acute/metabolism/pathology[MESH] |Male[MESH] |Megakaryocytes/cytology/*metabolism[MESH] |Mice[MESH] |Mice, Knockout[MESH] |NF-kappa B/genetics/metabolism[MESH] |ORAI1 Protein[MESH] |Phosphorylation[MESH] |Platelet Aggregation[MESH] |Protein Serine-Threonine Kinases/*physiology[MESH] |RNA, Messenger/genetics[MESH] |Reverse Transcriptase Polymerase Chain Reaction[MESH]The serum- and glucocorticoid-inducible kinase 1 (SGK1) influences pla(epmc).pdf DeepDyve Pubget Overpricing