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

Signaling by Eph receptors and cell-surface ephrin ligands modulates adhesive cell properties and thereby coordinates cell movement and positioning in normal and oncogenic development. While cell contact–dependent Eph activation frequently leads to cell-cell repulsion, also the diametrically opposit...

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Bibliographic Details
Published in:Blood 2008-08, Vol.112 (3), p.721-732
Main Authors: Wimmer-Kleikamp, Sabine H., Nievergall, Eva, Gegenbauer, Kristina, Adikari, Samantha, Mansour, Mariam, Yeadon, Trina, Boyd, Andrew W., Patani, Neill R., Lackmann, Martin
Format: Article
Language:English
Subjects:
Cell Adhesion
Cell Line
Cell Line, Tumor
Cell Polarity
Cell Shape
Ephrin-A5 - physiology
Ephrins - physiology
Humans
Phosphorylation
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology
Protein Tyrosine Phosphatases - metabolism
Receptor, EphA3 - physiology
Receptors, Eph Family - physiology
Signal Transduction
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Summary:Signaling by Eph receptors and cell-surface ephrin ligands modulates adhesive cell properties and thereby coordinates 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-biologic mechanisms underlying this switch by analyzing ephrin-A5–induced cell-morphologic changes of EphA3-positive LK63 pre-B acute lymphoblastic leukemia cells. Their exposure to ephrin-A5 surfaces leads to a rapid conversion from a suspended/nonpolarized to an adherent/polarized cell type, a transition that relies on EphA3 functions operating in the absence of Eph-kinase signaling. 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 signaling reverse the phenotype to nonadherent 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 hematopoietic tumors.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2007-11-121681