Document Detail

Cell-specific information processing in segregating populations of Eph receptor ephrin-expressing cells.
MedLine Citation:
PMID:  20007894     Owner:  NLM     Status:  MEDLINE    
Cells have self-organizing properties that control their behavior in complex tissues. Contact between cells expressing either B-type Eph receptors or their transmembrane ephrin ligands initiates bidirectional signals that regulate cell positioning. However, simultaneously investigating how information is processed in two interacting cell types remains a challenge. We implemented a proteomic strategy to systematically determine cell-specific signaling networks underlying EphB2- and ephrin-B1-controlled cell sorting. Quantitative mass spectrometric analysis of mixed populations of EphB2- and ephrin-B1-expressing cells that were labeled with different isotopes revealed cell-specific tyrosine phosphorylation events. Functional associations between these phosphotyrosine signaling networks and cell sorting were established with small interfering RNA screening. Data-driven network modeling revealed that signaling between mixed EphB2- and ephrin-B1-expressing cells is asymmetric and that the distinct cell types use different tyrosine kinases and targets to process signals induced by cell-cell contact. We provide systems- and cell-specific network models of contact-initiated signaling between two distinct cell types.
Claus Jørgensen; Andrew Sherman; Ginny I Chen; Adrian Pasculescu; Alexei Poliakov; Marilyn Hsiung; Brett Larsen; David G Wilkinson; Rune Linding; Tony Pawson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  326     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-17     Completed Date:  2010-01-12     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1502-9     Citation Subset:  IM    
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MeSH Terms
Adaptor Proteins, Signal Transducing / metabolism
Cell Line
Ephrin-B1 / genetics,  metabolism*
Mass Spectrometry
Models, Biological
PDZ Domains
Protein Binding
Protein Interaction Domains and Motifs
Protein-Tyrosine Kinases / metabolism
RNA, Small Interfering
Receptor, EphB2 / genetics,  metabolism*
Signal Transduction*
Tyrosine / metabolism
src Homology Domains
Grant Support
MC_U117532048//Medical Research Council; MOP-6849//Canadian Institutes of Health Research
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Ephrin-B1; 0/Ligands; 0/RNA, Small Interfering; 42HK56048U/Tyrosine; EC Kinases; EC, EphB2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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