PMID- 20813958
OWN - NLM
STAT- MEDLINE
DCOM- 20101102
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 107
IP  - 38
DP  - 2010 Sep 21
TI  - Distribution of resting and ligand-bound ErbB1 and ErbB2 receptor tyrosine 
      kinases in living cells using number and brightness analysis.
PG  - 16524-9
LID - 10.1073/pnas.1002642107 [doi]
AB  - Ligand-driven dimerizations of ErbB receptor subunits fulfill a fundamental role 
      in their activation. We have used the number and brightness analysis technique to 
      investigate the existence of preformed ligand-independent dimers and clusters and 
      to characterize the initial steps in the activation of ErbB1 and ErbB2. In cells 
      expressing 50,000-200,000 receptors, ErbB1 was monomeric in the absence of ligand 
      stimulation, whereas in CHO cells with receptor levels >500,000 as much as 30% of 
      ErbB1 was present as preformed dimers. EGF induced the formation of ErbB1 dimers 
      as well as larger clusters (up to pentamers) that colocalized with 
      clathrin-coated pits. The distribution of unstimulated ErbB2 in cells expressing 
      3.10(5)-10(6) receptors was fundamentally different, in that this receptor was 
      present in preformed homoassociated aggregates containing 5-10 molecules. These 
      constitutive ErbB2 homoclusters colocalized with caveolae, increased in size at 
      subphysiological temperatures, but decreased in size upon EGF stimulation. We 
      conclude that these ErbB2 clusters are promoted primarily by membrane-mediated 
      interactions and are dispersed upon ligand stimulation.
FAU - Nagy, Peter
AU  - Nagy P
AD  - Laboratory of Cellular Dynamics, Max Planck Institute for Biophysical Chemistry, 
      Am Fassberg 11, D-37077 Gottingen, Germany.
FAU - Claus, Jeroen
AU  - Claus J
FAU - Jovin, Thomas M
AU  - Jovin TM
FAU - Arndt-Jovin, Donna J
AU  - Arndt-Jovin DJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100902
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Ligands)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - CHO Cells
MH  - Cricetinae
MH  - Cricetulus
MH  - Epidermal Growth Factor/pharmacology
MH  - ErbB Receptors/chemistry/genetics/*metabolism
MH  - Green Fluorescent Proteins/chemistry/genetics/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Ligands
MH  - Luminescent Proteins/chemistry/genetics/metabolism
MH  - Mice
MH  - Microscopy, Fluorescence
MH  - Plasmids/genetics
MH  - Protein Multimerization/drug effects
MH  - Protein Structure, Quaternary/drug effects
MH  - Receptor, ErbB-2/chemistry/genetics/*metabolism
MH  - Recombinant Fusion Proteins/chemistry/genetics/metabolism
MH  - Signal Transduction
MH  - Transfection
PMC - PMC2944731
COIS- The authors declare no conflict of interest.
EDAT- 2010/09/04 06:00
MHDA- 2010/11/03 06:00
PMCR- 2010/09/02
CRDT- 2010/09/04 06:00
PHST- 2010/09/04 06:00 [entrez]
PHST- 2010/09/04 06:00 [pubmed]
PHST- 2010/11/03 06:00 [medline]
PHST- 2010/09/02 00:00 [pmc-release]
AID - 1002642107 [pii]
AID - 201002642 [pii]
AID - 10.1073/pnas.1002642107 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16524-9. doi: 
      10.1073/pnas.1002642107. Epub 2010 Sep 2.