OpenSSL SSL_connect: Connection reset by peer in connection to v2.sherpa.ac.uk:443 PuSH - Publication Server of Helmholtz Zentrum München: Subcellular fractionation of TGF-β1-stimulated lung epithelial cells: A novel proteomic approach for identifying signaling intermediates.

PuSH - Publication Server of Helmholtz Zentrum München

Milosevic, J.* ; Bulau, P.* ; Mortz, E.* ; Eickelberg, O.

Subcellular fractionation of TGF-β1-stimulated lung epithelial cells: A novel proteomic approach for identifying signaling intermediates.

Proteomics 9, 1230-1240 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Members of the transforming growth factor (TGF)-beta superfamily are key regulators of lung development and homeostasis, in particular by controlling alveolar/bronchial epithelial cell function. TGF-beta signaling involves ligand-dependent activation of receptor serine/threonine kinases, activation and subsequent nuclear translocation of pathway-specific transcription factors (Smads), and ultimately, modulation of gene expression. While Smad-dependent responses represent the primary signaling components activated by TGF-beta receptors, their function is controlled by a variety of cofactors. In addition, alternative signaling systems mediating TGF-beta-induced effects have recently been described such as MAP kinase pathways. To uncover novel proteins that participate in TGF-beta signaling via nuclear/cytoplasmic shuttling in lung epithelial cells, we have analyzed A549 human lung epithelial cells, using subcellular fractionation combined with 2-D PAGE, tryptic digestion, and MS. We identified a rapid increase in the cytosolic localization of KH-type splicing regulatory protein (KHSRP), far upstream element-binding protein (FUBP1), hnRNP-L, and hnRNP-H1, concomitant with a decrease in their nuclear localization in response to TGF-beta 1. Proteomic data were confirmed by immunofluorescence and immunoblot analyses. In summary, we represent a powerful novel technology for the identification of previously unknown signaling intermediates.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cell differentiation; Cytosol; Lung epithelium; Lung fibrosis; TGF-beta; growth-factor-beta; rna-binding-proteins; far upstream element; heat-shock proteins; messenger-rna; molecular chaperones; c-myc; family; identification; inhibition
ISSN (print) / ISBN 1615-9853
e-ISSN 1615-9861
Journal Proteomics
Quellenangaben Volume: 9, Issue: 5, Pages: 1230-1240 Article Number: , Supplement: ,
Publisher Wiley
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)