Effect of TGFß on calcium signaling in megakaryocytes.
Biochem Biophys Res Commun
; 461(1): 8-13, 2015 May 22.
Article
em En
| MEDLINE
| ID: mdl-25849886
ABSTRACT
TGFß is a powerful regulator of megakaryocyte maturation and platelet formation. As previously shown for other cell types, TGFß may up-regulate the expression of the serum & glucocorticoid inducible kinase SGK1, an effect requiring p38 kinase. SGK1 has in turn recently been shown to participate in the regulation of cytosolic Ca(2+) activity ([Ca(2+)]i) in megakaryocytes and platelets. SGK1 phosphorylates the IκB kinase (IKKα/ß), which in turn phosphorylates the inhibitor protein IκBα resulting in nuclear translocation of nuclear factor NFκB. Genes up-regulated by NFκB include Orai1, the pore forming ion channel subunit accomplishing store operated Ca(2+) entry (SOCE). The present study explored whether TGFß influences Ca(2+) signaling in megakaryocytes. [Ca(2+)]i was determined by Fura-2 fluorescence and SOCE from the increase of [Ca(2+)]i following re-addition of extracellular Ca(2+) after store depletion by removal of extracellular Ca(2+) and inhibition of the sarcoendoplasmatic Ca(2+) ATPase (SERCA) with thapsigargin (1 µM). As a result, TGFß (60 ng, 24 h) increased SOCE, an effect significantly blunted by p38 kinase inhibitor Skepinone-L (1 µM), SGK1 inhibitor EMD638683 (50 µM) and NFκB inhibitor wogonin (100 µM). In conclusion, TGFß is a powerful regulator of store operated Ca(2+) entry into megakaryocytes, an effect mediated by a signaling cascade involving p38 kinase, SGK1 and NFκB.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Megacariócitos
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Cálcio
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Fator de Crescimento Transformador beta
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Sinalização do Cálcio
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article