MyJournals Home  

RSS FeedsTransforming growth factor {beta} (TGF{beta}) induces NUAK kinase expression to fine-tune its signaling output [Cell Biology] (Journal of Biological Chemistry)


15 march 2019 09:02:32

Transforming growth factor {beta} (TGF{beta}) induces NUAK kinase expression to fine-tune its signaling output [Cell Biology] (Journal of Biological Chemistry)

TGF? signaling via SMAD proteins and protein kinase pathways up- or down-regulates the expression of many genes and thus affects physiological processes, such as differentiation, migration, cell cycle arrest, and apoptosis, during developmental or adult tissue homeostasis. We here report that NUAK family kinase 1 (NUAK1) and NUAK2 are two TGF? target genes. NUAK1/2 belong to the AMP-activated protein kinase (AMPK) family, whose members control central and protein metabolism, polarity, and overall cellular homeostasis. We found that TGF?-mediated transcriptional induction of NUAK1 and NUAK2 requires SMAD family members 2, 3, and 4 (SMAD2/3/4) and mitogen-activated protein kinase (MAPK) activities, which provided immediate and early signals for the transient expression of these two kinases. Genomic mapping identified an enhancer element within the first intron of the NUAK2 gene that can recruit SMAD proteins, which, when cloned, could confer induction by TGF?. Furthermore, NUAK2 formed protein complexes with SMAD3 and the TGF? type I receptor. Functionally, NUAK1 suppressed and NUAK2 induced TGF? signaling. This was evident during TGF?-induced epithelial cytostasis, mesenchymal differentiation, and myofibroblast contractility, in which NUAK1 or NUAK2 silencing enhanced or inhibited these responses, respectively. In conclusion, we have identified a bifurcating loop during TGF? signaling, whereby transcriptional induction of NUAK1 serves as a negative checkpoint and NUAK2 induction positively contributes to signaling and terminal differentiation responses to TGF? activity. Digg Facebook Google StumbleUpon Twitter
23 viewsCategory: Biochemistry
A high-throughput chemical-genetics screen in murine adipocytes identifies insulin-regulatory pathways [Cell Biology] (Journal of Biological Chemistry)
A stable tetramer is not the only oligomeric state that mitochondrial single-stranded DNA binding proteins can adopt [DNA and Chromosomes] (Journal of Biological Chemistry)
blog comments powered by Disqus
The latest issues of all your favorite science journals on one page


Register | Retrieve



Use these buttons to bookmark us: Digg Facebook Google StumbleUpon Twitter

Valid HTML 4.01 Transitional
Copyright © 2008 - 2019 Indigonet Services B.V.. Contact: Tim Hulsen. Read here our privacy notice.
Other websites of Indigonet Services B.V.: Nieuws Vacatures News Tweets Travel Photos Nachrichten Indigonet Finances Leer Mandarijn