TABLE 4

G protein-coupled receptors interacting with NHERF proteins

GPCRPDZ-Binding MotifNHERF TargetFunctionReference
PTHRE-T-V-MPDZ1 NHERF1s, Gαq, Gαi, PLCβ, PKA, PKC, MAP kinase signalingMahon et al., 2002; Sneddon et al., 2003; Mahon and Segre, 2004; Wang et al., 2007
PDZ2 NHERF2Receptor trafficking & desensitizationWheeler et al., 2008
Npt2a regulationWang et al., 2008, 2009, 2010; Weinman et al., 2009, 2011
β2-ARD-S-L-LPDZ1 NHERF1NHE3 & CFTR regulationHall et al., 1998; Naren et al., 2003; Taouil et al., 2003; Singh et al., 2009
PDZ1,2 NHERF2
PDZ2 NHERF3
κORN-K-P-VPDZ1 NHERF1Receptor recyclingLi et al., 2002
NHE3 regulationHuang et al., 2004; Liu-Chen, 2004
mGluR5S-S-S-LPDZ2 NHERF2Prolong calcium mobilizationPaquet et al., 2006
Potentiate cell death
P2Y1D-T-S-LPDZ1 NHERF1PLCβ signalingHall et al., 1998
AKAP activity (via ezrin)Fam et al., 2005
PDZ1, PDZ2 NHERF2CFTR regulationGuerra et al., 2004
Receptor dimerizationChoi et al., 2008
LPA2 (LPA5)D-S-T-LPDZ2 NHERF2q, Gαi, PLCβ, Akt, MAP kinase signalingOh et al., 2004
Choi et al., 2010
CFTR regulation (LPA5: NHE3)Li et al., 2005; Singh et al., 2009
Antiapoptotic signalingYun et al., 2005; E et al., 2009; Lee et al., 2011
Cell migrationCha et al., 2010; Lin et al., 2010
CCR5S-V-G-LPDZ2 NHERF1Receptor internalization & dimerizationHammad et al., 2010
MAP kinase signaling
CLRLD-T-L-LPDZ1 NHERF1Receptor internalizationBomberger et al., 2005a,b
RAMP3
A2b?NHERF2Membrane anchoringSitaraman et al., 2002
TXA2IndirectPDZ 1&2 NHERF1q & PLCβ signalingRochdi et al., 2002; Rochdi and Parent, 2003
Fzd (Fzd4)X-S/T-X-V/L (ETVV)PDZ2 NHERF2Wnt/β-catenin signaling Tumor suppressor in breast cancerWheeler et al., 2011
  • MAP, mitogen-activated protein; AKAP, A kinase anchoring protein; Akt, protein kinase B.