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Blood, 1 August 2008, Vol. 112, No. 3, pp. 721-732. Prepublished online as a Blood First Edition Paper on April 2, 2008; DOI 10.1182/blood-2007-11-121681. This Article Full Text Full Text (PDF) Supplemental Figures and Videos All Versions of this Article: blood-2007-11-121681v1 112/3/721    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wimmer-Kleikamp, S. H. Articles by Lackmann, M. Search for Related Content PubMed PubMed Citation Articles by Wimmer-Kleikamp, S. H. Articles by Lackmann, M. Related Collections Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Elevated protein tyrosine phosphatase activity provokes Eph/ephrin-facilitated adhesion of pre-B leukemia cells Sabine H. Wimmer-Kleikamp1,*, Eva Nievergall1,*, Kristina Gegenbauer1, Samantha Adikari1, Mariam Mansour1, Trina Yeadon2, Andrew W. Boyd2, Neill R. Patani3, and Martin Lackmann1 1 Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia; 2 Leukemia Foundation Cancer Research Unit, Queensland Institute of Medical Research, Brisbane, Australia; and 3 Division of Surgical and Interventional Sciences, Royal Free & University College Medical School, London, United Kingdom 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: PTPases: "Eph" ective arbitrators of attraction Bing-Cheng Wang Blood 2008 112: 455-456. [Full Text] [PDF] This article has been cited by other articles: M. Lackmann and A. W. Boyd Eph, a Protein Family Coming of Age: More Confusion, Insight, or Complexity? Sci. Signal., April 15, 2008; 1(15): re2 - re2. [Abstract] [Full Text] [PDF]

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