Signalling by Eph receptors and cell-surface ephrin ligands modulates adhesive cell properties and thereby co-ordinates cell movement and positioning in normal and oncogenic development. While cell-contact dependent Eph activation frequently leads to cell-cell repulsion, also the diametrically-opposite response, cell-cell adhesion, is a probable outcome. However, the molecular principles regulating such disparate functions have remained controversial. We have examined cell-biological mechanisms underlying this switch by analysing ephrin-A5 induced cell morphological changes of EphA3-positive LK63 pre-B acute lymphoblastic leukaemia cells. Their exposure to ephrin-A5 surfaces leads to a rapid conversion from a suspended/nonpolarized to adherent/polarized cell type, a transition which relies on EphA3 functions operating in the absence of Eph-kinase signalling. Cell morphology change and adhesion of LK63 cells are effectively attenuated by endogenous protein tyrosine phosphatase (PTP) activity, whereby PTP inhibition and productive EphA3-phosphotyrosine signalling reverse the phenotype to non-adherent cells with a condensed cytoskeleton. Our findings suggest that Eph-associated PTP activities not only control receptor phosphorylation levels, but as a result switch the response to ephrin-contact from repulsion to adhesion, which may play a role in the pathology of haematopoietic tumours.
|Pages (from-to)||721 - 732|
|Number of pages||12|
|Publication status||Published - 2008|