PMID- 15161943
OWN - NLM
STAT- MEDLINE
DCOM- 20051207
LR  - 20171116
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 117
IP  - Pt 14
DP  - 2004 Jun 15
TI  - A NHERF binding site links the betaPDGFR to the cytoskeleton and regulates cell 
      spreading and migration.
PG  - 2951-61
AB  - The Na(+)/H(+) exchanger regulatory factor, NHERF, is a multifunctional adapter 
      protein involved in a wide range of physiological activities. NHERF associates 
      with merlin and the ezrin/radixin/moesin (MERM) family of membrane-actin 
      cytoskeletal linker proteins through its C-terminus and is capable of interacting 
      via its PDZ1 domain to the betaPDGF receptor (betaPDGFR). Thus, NHERF, 
      potentially links the betaPDGFR to the actin cytoskeleton through its interaction 
      with MERM proteins. In the present study, we have examined whether abolishing the 
      interaction of betaPDGFR with NHERF results in actin cytoskeletal rearrangements. 
      We have stably expressed a wild-type betaPDGFR, a mutant betaPDGFR (L1106A) that 
      is incapable of interacting with NHERF, as well as a kinase defective mutant 
      receptor (K634R), in PDGFR-deficient mouse embryonic fibroblasts. Our 
      observations indicate that cells expressing betaPDGFR (L1106A) were impaired in 
      their ability to spread and migrate on fibronectin compared with wild-type and 
      K634R cells. L1106A mutant cells also revealed an increased number of focal 
      adhesions, a condensed F-actin ring at the cell periphery and a decrease in total 
      focal adhesion kinase (FAK) tyrosine phosphorylation. Further, we show that NHERF 
      and MERM proteins could act as intermediary bridging proteins between betaPDGFR 
      and FAK. Thus, the interaction of betaPDGFR with NHERF may provide an essential 
      link between the cell membrane and the cortical actin cytoskeleton independent of 
      receptor activity.
FAU - James, Marianne F
AU  - James MF
AD  - Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts 
      General Hospital, Building 149, 13th Street, Charlestown, MA 02129, USA.
FAU - Beauchamp, Roberta L
AU  - Beauchamp RL
FAU - Manchanda, Nitasha
AU  - Manchanda N
FAU - Kazlauskas, Andrius
AU  - Kazlauskas A
FAU - Ramesh, Vijaya
AU  - Ramesh V
LA  - eng
GR  - NS24279/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040525
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Actins)
RN  - 0 (Neurofibromin 2)
RN  - 0 (Phosphoproteins)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Sodium-Hydrogen Exchangers)
RN  - 0 (sodium-hydrogen exchanger regulatory factor)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Binding Sites
MH  - Cell Line
MH  - Cell Membrane/metabolism
MH  - Cell Movement/*physiology
MH  - Cell Shape/physiology
MH  - Cytoskeleton/*metabolism
MH  - Focal Adhesions/metabolism
MH  - Humans
MH  - Mice
MH  - Mutation
MH  - Neurofibromin 2/metabolism
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Platelet-Derived Growth Factor/physiology
MH  - Receptor, Platelet-Derived Growth Factor beta/genetics/*metabolism
MH  - Sodium-Hydrogen Exchangers
MH  - Tyrosine/metabolism
EDAT- 2004/05/27 05:00
MHDA- 2005/12/13 09:00
CRDT- 2004/05/27 05:00
PHST- 2004/05/27 05:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2004/05/27 05:00 [entrez]
AID - jcs.01156 [pii]
AID - 10.1242/jcs.01156 [doi]
PST - ppublish
SO  - J Cell Sci. 2004 Jun 15;117(Pt 14):2951-61. doi: 10.1242/jcs.01156. Epub 2004 May 
      25.