Comparison of WNK4 and WNK1 kinase and inhibiting activities

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

WNK kinases are novel serine/threonine protein kinases. Mutations in two members of the WNK family, WNK1 and WNK4, cause familial hyperkalemic hypertension. These kinases regulate ion transport across diverse epithelia; WNK4 reduces activity of the Na-Cl cotransporter activity and the potassium channel, ROMK, by reducing their appearance at the plasma membrane. We examined the kinase activity of WNK1 and WNK4 in vitro. A glutathione S-transferase (GST) fusion protein of the WNK1 kinse domain phosphorylated itself and a substrate protein, as reported previously. A longer construct, containing the autoinhibitory domain, did not. A GST WNK4 kinase domain construct demonstrated no kinase activity, in vitro or in HEK 293 cells. WNK4 constructs that included a region homologous to the autoinhibitory domain of WNK1 inhibited WNK1 kinase activity. Inhibition by a short WNK4 segment, WNK4 (444-518), was greater than inhibition by WNK4 (444-563). Together, these results suggest that WNK4 must be activated by currently unknown factors to exhibit kinase activity and that WNK4 contains an inhibitory domain that can inhibit the kinase activity of WNK1.

Original languageEnglish (US)
Pages (from-to)939-944
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume317
Issue number3
DOIs
StatePublished - May 7 2004

Fingerprint

Phosphotransferases
Glutathione Transferase
Member 3 Solute Carrier Family 12
HEK293 Cells
Protein-Serine-Threonine Kinases
Potassium Channels
Ion Transport
Cell membranes
Proteins
Fusion reactions
Epithelium
Cell Membrane
Ions
Hypertension
Mutation
Substrates

Keywords

  • Chloride transport
  • Distal convoluted tubule
  • Distal tubule
  • Kidney
  • Serine/threonine kinases
  • Sodium chloride transporter
  • WNK kinases

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Comparison of WNK4 and WNK1 kinase and inhibiting activities. / Wang, Zhaohong; Yang, Chao-Ling; Ellison, David.

In: Biochemical and Biophysical Research Communications, Vol. 317, No. 3, 07.05.2004, p. 939-944.

Research output: Contribution to journalArticle

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