Biological cross-talk between WNK1 and the transforming growth factor β-Smad signaling pathway

Byung Hoon Lee, Wei Chen, Steve Stippec, Melanie H. Cobb

Research output: Contribution to journalArticle

38 Scopus citations

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 languageEnglish (US)
Pages (from-to)17985-17996
Number of pages12
JournalJournal of Biological Chemistry
Volume282
Issue number25
DOIs
StatePublished - Jun 22 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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