Elevated protein tyrosine phosphatase activity provokes Eph/ephrin-facilitated adhesion of pre-B leukemia cells

Sabine H Wimmer-Kleikamp, Eva Nievergall, Kristina Gegenbauer, Samantha Hiroshini Adikari, Mariam Mansour, Trina Yeadon, Andrew W Boyd, Neill R Patani, Martin Lackmann

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44 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)721 - 732
Number of pages12
JournalBlood
Volume112
Issue number3
Publication statusPublished - 2008

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