Open AccessP38 Kinase, SGK1 and NF-κB Dependent Up-Regulation of Na+/Ca2+ Exchanger Expression and Activity Following TGFß1 Treatment of Megakaryocytes
Author(s) -
Tamer AlMaghout,
Lisann Pelzl,
Itishri Sahu,
Basma Sukkar,
Zohreh Hosseinzadeh,
Ravi Kumar Gutti,
Stefan Laufer,
Jakob Voelkl,
Burkert Pieske,
Meinrad Gawaz,
Florian Läng
Publication year - 2017
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000479992
Subject(s) - extracellular , sgk1 , thapsigargin , cytosol , orai1 , chemistry , kinase , sodium calcium exchanger , transforming growth factor , signal transduction , intracellular , growth factor , microbiology and biotechnology , endocrinology , medicine , biology , endoplasmic reticulum , stim1 , biochemistry , receptor , enzyme
TGFβ1, a decisive regulator of megakaryocyte maturation and platelet formation, has previously been shown to up-regulate both, store operated Ca2+ entry (SOCE) and Ca2+ extrusion by Na+/Ca2+ exchange. The growth factor thus augments the increase of cytosolic Ca2+ activity ([Ca2+]i) following release of Ca2+ from intracellular stores and accelerates the subsequent decline of [Ca2+]i. The effect on SOCE is dependent on a signaling cascade including p38 kinase, serum & glucocorticoid inducible kinase SGK1, and nuclear factor NFκB. The specific Na+/Ca2+ exchanger isoforms involved and the signalling regulating the Na+/Ca2+ exchangers remained, however elusive. The present study explored, whether TGFβ1 influences the expression and function of K+ insensitive (NCX) and K+ sensitive (NCKX) Na+/Ca2+ exchangers, and aimed to shed light on the signalling involved.