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EphrinB1 signals from the cell surface to the nucleus by recruitment of STAT3

  1. Author:
    Bong, Y. S.
    Lee, H. S.
    Carim-Todd, L.
    Mood, K.
    Nishanian, T. G.
    Tessarollo, L.
    Daar, I. O.
  2. Author Address

    Natl Canc Inst, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. Natl Canc Inst, Mouse Canc Genet Program, Frederick, MD 21702 USA.;Daar, IO, Natl Canc Inst, Lab Cell & Dev Signaling, Bldg 560, Frederick, MD 21702 USA.;daar@ncifcrf.gov
    1. Year: 2007
    2. Date: Oct
  1. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 104
    2. 44
    3. Pages: 17305-17310
  2. Type of Article: Article
  3. ISSN: 0027-8424
  1. Abstract:

    The Eph (erythropoietin-producing hepatoma) family of receptor tyrosine kinases and their membrane-bound ligands, the ephrins, have been implicated in regulating cell adhesion and migration during development by mediating cell-to-cell signaling events. The transmembrane ephrinB (Eph receptor interactor B) protein is a bidirectional signaling molecule that sends a forward signal through the activation of its cognate receptor tyrosine kinase, residing on another cell. A reverse signal can be transduced into the ephrinB expressing cell via tyrosine phosphorylation of its conserved C-terminal cytoplasmic domain. Although some insight has been gained regarding how ephrinB may send signals affecting cytoskeletal components, little is known about how ephrinBl reverse signaling affects transcriptional processes. Here we report that signal transducer and activator of transcription 3 (STAT3) can interact with ephrinB1 in a phosphorylation-dependent manner that leads to enhanced activation of STAT3 transcriptional activity. This activity depends on the tyrosine kinase Jak2, and two tyrosines within the intracellular domain of ephrinB1 are critical for the association with STAT3 and its activation. The recruitment of STAT3 to ephrinBl, and its resulting Jak2-dependent activation and transcription of reporter targets, reveals a signaling pathway from ephrinBl to the nucleus.

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External Sources

  1. DOI: 10.1073/pnas.0702337104
  2. WOS: 000250638400016

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