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Extracellular ligation-dependent CD45RB enzymatic activity negatively regulates lipid raft signal transduction

Parikh, K., Poppema, S., Peppelenbosch, M. P. & Visser, L., 15-Jan-2009, In : Blood. 113, 3, p. 594-603 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Kaushal Parikh
  • Sibrand Poppema
  • Maikel P. Peppelenbosch
  • Lydia Visser

CD45 is the most prominent membrane protein on lymphocytes. The function and regulation of this protein tyrosine phosphatase remain largely obscure, mainly because of the lack of a known ligand, and it still remains unknown whether such tyrosine phosphatases are subject to extracellular control at all. We report that an anti-CD45RB antibody (Ab) that prevents rejection and induces tolerance activates CD45RB tyrosine phosphatase enzymatic activity in T lymphocytes, allowing us to directly monitor the effects of increased CD45RB activity on signal transduction. Using both kinase substrate peptide arrays as well as conventional biochemistry, we also provide evidence of the various kinases involved in bringing about the inhibitory effect of this Ab on CD3-induced T-cell receptor signaling. Furthermore, we report that activated CD45RB translocates to lipid rafts and interferes with lipid raft localization and activation state of CD45 substrate Lck. Thus, these findings indeed prove that CD45 is subject to extracellular control and also define a novel mechanism by which receptor tyrosine phosphatases control lymphocyte biology and provide further insight into the intracellular signaling pathways effected by anti-CD45RB monoclonal Ab treatment. (Blood. 2009; 113: 594-603)

Original languageEnglish
Pages (from-to)594-603
Number of pages10
JournalBlood
Volume113
Issue number3
Publication statusPublished - 15-Jan-2009

    Keywords

  • PROTEIN-TYROSINE PHOSPHATASES, SRC-FAMILY KINASES, T-CELL, TRANSPLANTATION TOLERANCE, LYMPHOCYTE-ACTIVATION, MONOCLONAL-ANTIBODIES, CYTOPLASMIC DOMAIN, ALLOGRAFT SURVIVAL, CUTTING EDGE, B-CELL

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