Abstract
WNKs (with no lysine (K)), unique serine/threonine protein kinases, have been best studied in the context of cell volume regulation and ion homeostasis. Here we describe a biological link between WNKs and transforming growth factor (TGF) β-Smad signaling. Both WNK1 and WNK4 directly bind to and phosphorylate Smad2. Knockdown of WNK1 in HeLa cells using small interfering RNA reduces Smad2 protein expression; this decrease is at least partially due to down-regulation of Smad2 transcription. In contrast, phosphorylated Smad2 significantly accumulated in the nucleus as a consequence of depletion of WNK1, resulting in Smad-mediated transcriptional responses. In addition, TGFβ-induced target gene transcripts were increased in WNK1 small interfering RNA cells. These findings suggest WNK1 as a dual modulator of TGFβ-Smad signaling pathways.
Original language | English (US) |
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Pages (from-to) | 17985-17996 |
Number of pages | 12 |
Journal | Journal of Biological Chemistry |
Volume | 282 |
Issue number | 25 |
DOIs | |
State | Published - Jun 22 2007 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology