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J. Biol. Chem., Vol. 276, Issue 9, 6689-6694, March 2, 2001
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From the Department of Physical Biology, Max Planck Institute for
Developmental Biology, Spemannstrasse 35, 72076 Tübingen,
Germany
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
An ephrin-A-dependent Signaling Pathway
Controls Integrin Function and Is Linked to the Tyrosine
Phosphorylation of a 120-kDa Protein*
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 1-dependent cell adhesion.
*
This work was supported in part by grants from the Deutsche
Forschungsgemeinschaft (to U. D.)The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: MRC Centre for
Developmental Neurobiology, King's College London, 4th Floor, New Hunt's House, Guy's Campus, London SE1 1UL, United Kingdom. Tel.: 0044-20-7848-6411; Fax: 0044-20-7848-6798; E-mail:
uwe.drescher@kcl.ac.uk.
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