PMID- 21615688
OWN - NLM
STAT- MEDLINE
DCOM- 20110913
LR  - 20201209
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Linking)
VI  - 278
IP  - 15
DP  - 2011 Aug
TI  - Identification of mitogen-activated protein/extracellular signal-responsive 
      kinase kinase 2 as a novel partner of the scaffolding protein human homolog of 
      disc-large.
PG  - 2655-65
LID - 10.1111/j.1742-4658.2011.08192.x [doi]
AB  - Human disc-large homolog (hDlg), also known as synapse-associated protein 97, is 
      a scaffold protein, a member of the membrane-associated guanylate kinase family, 
      implicated in neuronal synapses and epithelial-epithelial cell junctions whose 
      expression and function remains poorly characterized in most tissues, 
      particularly in the vasculature. In human vascular tissues, hDlg is highly 
      expressed in smooth muscle cells (VSMCs). Using the yeast two-hybrid system to 
      screen a human aorta cDNA library, we identified mitogen-activated 
      protein/extracellular signal-responsive kinase (ERK) kinase (MEK)2, a member of 
      the ERK cascade, as an hDlg binding partner. Site-directed mutagenesis showed a 
      major involvement of the PSD-95, disc-large, ZO-1 domain-2 of hDlg and the 
      C-terminal sequence RTAV of MEK2 in this interaction. Coimmunoprecipitation 
      assays in both human VSMCs and human embryonic kidney 293 cells, demonstrated 
      that endogenous hDlg physically interacts with MEK2 but not with MEK1. Confocal 
      microscopy suggested a colocalization of the two proteins at the inner layer of 
      the plasma membrane of confluent human embryonic kidney 293 cells, and in a 
      perinuclear area in human VSMCs. Additionally, hDlg also associates with the 
      endoplasmic reticulum and microtubules in these latter cells. Taken together, 
      these findings allow us to hypothesize that hDlg acts as a MEK2-specific scaffold 
      protein for the ERK signaling pathway, and may improve our understanding of how 
      scaffold proteins, such as hDlg, differentially tune MEK1/MEK2 signaling and cell 
      responses.
CI  - (c) 2011 The Authors Journal compilation (c) 2011 FEBS.
FAU - Maiga, Oumou
AU  - Maiga O
AD  - INSERM U698, Universite Paris 7, France.
FAU - Philippe, Monique
AU  - Philippe M
FAU - Kotelevets, Larissa
AU  - Kotelevets L
FAU - Chastre, Eric
AU  - Chastre E
FAU - Benadda, Samira
AU  - Benadda S
FAU - Pidard, Dominique
AU  - Pidard D
FAU - Vranckx, Roger
AU  - Vranckx R
FAU - Walch, Laurence
AU  - Walch L
LA  - eng
PT  - Journal Article
DEP - 20110613
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (DLG1 protein, human)
RN  - 0 (Discs Large Homolog 1 Protein)
RN  - 0 (Membrane Proteins)
RN  - EC 2.7.1.- (MAP2K2 protein, human)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 2)
RN  - EC 2.7.12.2 (MAP2K1 protein, human)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - Cell Membrane/enzymology
MH  - Discs Large Homolog 1 Protein
MH  - Endoplasmic Reticulum/enzymology
MH  - HEK293 Cells
MH  - Humans
MH  - MAP Kinase Kinase 1/metabolism
MH  - MAP Kinase Kinase 2/*metabolism
MH  - Membrane Proteins/*metabolism
MH  - Microtubules/enzymology
MH  - Muscle, Smooth, Vascular/cytology
MH  - Signal Transduction/genetics
MH  - Two-Hybrid System Techniques
EDAT- 2011/05/28 06:00
MHDA- 2011/09/14 06:00
CRDT- 2011/05/28 06:00
PHST- 2011/05/28 06:00 [entrez]
PHST- 2011/05/28 06:00 [pubmed]
PHST- 2011/09/14 06:00 [medline]
AID - 10.1111/j.1742-4658.2011.08192.x [doi]
PST - ppublish
SO  - FEBS J. 2011 Aug;278(15):2655-65. doi: 10.1111/j.1742-4658.2011.08192.x. Epub 
      2011 Jun 13.