An ephrin-A-dependent signaling pathway controls integrin function and is linked to the tyrosine phosphorylation of a 120-kDa protein.
The Eph family of receptor tyrosine kinases and their ligands, the ephrins, have been implicated in the development of the retinotectal projection. Here, glycosylphosphatidylinositol-anchored A-ephrins are not only expressed in the tectum but also on retinal axons, raising the possibility that they function in this context as receptors. We now show that activation of ephrin-A2 or ephrin-A5 by one of their receptors, ephA3, results in a beta 1-integrin-dependent increased adhesion of ephrin-A-expressing cells to laminin. In the search for an ephrin-A-dependent signaling pathway controlling integrin activation, we identified a 120-kDa raft membrane protein that is tyrosine-phosphorylated specifically after ephrin-A activation. Tyrosine phosphorylation of this protein is not seen after stimulating ephrin-A2-expressing cells with basic fibroblast growth factor, epidermal growth factor, insulin growth factor, or fetal calf serum containing a large set of different growth factors. The role of p120 as a mediator of an ephrin-A-integrin coupling is supported by the finding that inhibiting tyrosine phosphorylation of p120 correlates with an abolishment of the beta 1-dependent cell adhesion.
Huai
J
J
Department of Physical Biology, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen, Germany.
Drescher
U
U
D002448:Cell Adhesion; D002460:Cell Line; D036383:Ephrin-A2; D036386:Ephrin-A5; D006801:Humans; D016023:Integrins / Q000502:physiology*; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology*; D008970:Molecular Weight; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D036141:Receptor, EphA7; D014157:Transcription Factors / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism*
D036383:Ephrin-A2; D036386:Ephrin-A5; D016023:Integrins; D008565:Membrane Proteins; D014157:Transcription Factors; D014443:Tyrosine; D020794:Receptor Protein-Tyrosine Kinases; D036141:Receptor, EphA7