Cell-specific information processing in segregating populations of Eph receptor ephrin-expressing cells.
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.
Jørgensen
Claus
C
Samuel Lunenfeld Research Institute (SLRI), Mount Sinai Hospital, Toronto M5G 1X5, Canada.
Sherman
Andrew
A
Chen
Ginny I
GI
Pasculescu
Adrian
A
Poliakov
Alexei
A
Hsiung
Marilyn
M
Larsen
Brett
B
Wilkinson
David G
DG
Linding
Rune
R
Pawson
Tony
T
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000465:Algorithms; D002460:Cell Line; D036387:Ephrin-B1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D013058:Mass Spectrometry; D008954:Models, Biological; D054731:PDZ Domains; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D040901:Proteomics; D034741:RNA, Small Interfering; D036183:Receptor, EphB2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D036387:Ephrin-B1; D008024:Ligands; D034741:RNA, Small Interfering; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D036183:Receptor, EphB2