The Na+/H+exchanger regulatory factor 2 mediates phosphorylation of serum- and glucocorticoid-induced protein kinase 1 by 3-phosphoinositide-dependent protein kinase 1

Jaesun Chun, Taegun Kwon, Eunjung Lee, Pann Ghill Suh, Eui Ju Choi, Sang Sun Kang

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The Na+/H+ exchanger regulatory factor 2 (NHERF2/TKA-1/E3KARP) contains two PSD-95/Dlg/ZO-1 (PDZ) domains which interact with the PDZ docking motif (X-(S/T)-X-(V/L)) of proteins to mediate the assembly of transmembrane and cytosolic proteins into functional signal transduction complexes. One of the PDZ domains of NHERF2 interacts specifically with the DSLL, DSFL, and DTRL motifs present at the carboxy-termini of the 2-adrenergic receptor, the platelet-derived growth factor receptor, and the cystic fibrosis transmembrane conductance regulator, respectively. Serum- and glucocorticoid-induced protein kinase 1 (SGK1) also carries a putative PDZ-binding motif (D-S-F-L) at its carboxy tail, implicated in the specific interaction with NHERF2. There is a 3-phosphoinositide-dependent protein kinase 1 (PDK1) interacting fragment (PIF) in the tail of NHERF2. Using pull-down assays and co-transfection experiments, we demonstrated that the DSFL tail of SGK1 interacts with the first PDZ domain of NHERF2 and the PIF of NHERF2 binds to the PIF-binding pocket of PDK1 to form an SGK1-NHERF2-PDK1 complex. Formation of the protein complex promoted the phosphorylation and activation of SGK1 by PDK1. Thus, it was suggested that NHERF2 mediates the activation and phosphorylation of SGK1 by PDK1 through its first PDZ domain and PIF motif, as a novel SGK1 activation mechanism.

Original languageEnglish
Pages (from-to)207-215
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume298
Issue number2
DOIs
Publication statusPublished - 2002 Nov 18

Fingerprint

3-Phosphoinositide-Dependent Protein Kinases
Phosphorylation
Protein Kinases
Glucocorticoids
Proteins
Serum
Phosphatidylinositols
Chemical activation
sodium-hydrogen exchanger regulatory factor
Platelet-Derived Growth Factor Receptors
Cystic Fibrosis Transmembrane Conductance Regulator
Signal transduction
Adrenergic Receptors
Transfection
Assays
Signal Transduction

Keywords

  • 3-Phosphoinositide-dependent protein kinase 1
  • Na/H exchanger regulatory factors
  • PDK1 interacting fragment
  • PDZ domain
  • SGK1
  • SGK1 and PI3 kinase signal transduction pathways

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

The Na+/H+exchanger regulatory factor 2 mediates phosphorylation of serum- and glucocorticoid-induced protein kinase 1 by 3-phosphoinositide-dependent protein kinase 1. / Chun, Jaesun; Kwon, Taegun; Lee, Eunjung; Suh, Pann Ghill; Choi, Eui Ju; Sun Kang, Sang.

In: Biochemical and Biophysical Research Communications, Vol. 298, No. 2, 18.11.2002, p. 207-215.

Research output: Contribution to journalArticle

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