Ephrin-B1 transduces signals to activate integrin-mediated migration, attachment and angiogenesis.

Huynh-Do U, Vindis C, Liu H, Cerretti DP, McGrew JT, Enriquez M, Chen J, Daniel TO
J Cell Sci. 2002 115 (Pt 15): 3073-81

PMID: 12118063

Ephrin-B/EphB family proteins are implicated in bidirectional signaling and were initially defined through the function of their ectodomain sequences in activating EphB receptor tyrosine kinases. Ephrin-B1-3 are transmembrane proteins sharing highly conserved C-terminal cytoplasmic sequences. Here we use a soluble EphB1 ectodomain fusion protein (EphB1/Fc) to demonstrate that ephrin-B1 transduces signals that regulate cell attachment and migration. EphB1/Fc induced endothelial ephrin-B1 tyrosine phosphorylation, migration and integrin-mediated (alpha(v)beta(3) and alpha(5)beta(1)) attachment and promoted neovascularization, in vivo, in a mouse corneal micropocket assay. Activation of ephrin-B1 by EphB1/Fc induced phosphorylation of p46 JNK but not ERK-1/2 or p38 MAPkinases. By contrast, mutant ephrin-B1s bearing either a cytoplasmic deletion (ephrin-B1DeltaCy) or a deletion of four C-terminal amino acids (ephrin-B1DeltaPDZbd) fail to activate p46 JNK. Transient expression of intact ephin-B1 conferred EphB1/Fc migration responses on CHO cells, whereas the ephrin-B1DeltaCy and ephrin-B1DeltaPDZbd mutants were inactive. Thus ephrin-B1 transduces 'outside-in' signals through C-terminal protein interactions that affect integrin-mediated attachment and migration.

MeSH Terms (23)

Amino Acid Sequence Animals Cell Adhesion Cell Membrane Cell Movement CHO Cells Cornea Cricetinae Endothelium, Vascular Ephrin-B1 Humans Integrins Male MAP Kinase Signaling System Mice Mutation Neovascularization, Physiologic Organ Culture Techniques Phosphorylation Protein Structure, Tertiary Receptor, EphB1 Recombinant Fusion Proteins Signal Transduction

Connections (2)

This publication is referenced by other Labnodes entities:

Links