ephrinB1 signals from the cell surface to the nucleus by recruitment of STAT3

Yong Sik Bong, Hyun Shik Lee, Laura Carim-Todd, Kathleen Mood, Tagvor G. Nishanian, Lino Tessarollo, Ira O. Daar

Research output: Contribution to journalArticle

60 Scopus citations

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 ephrinB1 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 ephrinB1, and its resulting Jak2-dependent activation and transcription of reporter targets, reveals a signaling pathway from ephrinB1 to the nucleus.

Original languageEnglish (US)
Pages (from-to)17305-17310
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number44
DOIs
StatePublished - Oct 30 2007

Keywords

  • Eph receptor
  • Fgf receptor
  • Jak2
  • Neuroepithelial cells
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • General

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    Bong, Y. S., Lee, H. S., Carim-Todd, L., Mood, K., Nishanian, T. G., Tessarollo, L., & Daar, I. O. (2007). ephrinB1 signals from the cell surface to the nucleus by recruitment of STAT3. Proceedings of the National Academy of Sciences of the United States of America, 104(44), 17305-17310. https://doi.org/10.1073/pnas.0702337104