Eomesodermin requires transforming growth factor-beta/activin signaling and binds Smad2 to activate mesodermal genes

J Biol Chem. 2009 Jan 23;284(4):2397-408. doi: 10.1074/jbc.M808704200. Epub 2008 Nov 26.

Abstract

The T-box gene Eomesodermin (Eomes) is required for early embryonic mesoderm differentiation in mouse, frog (Xenopus laevis), and zebrafish, is important in late cardiac development in Xenopus, and for CD8+ T effector cell function in mouse. Eomes can ectopically activate many mesodermal genes. However, the mechanism by which Eomes activates transcription of these genes is poorly understood. We report that Eomes protein interacts with Smad2 and is capable of working in a non-cell autonomous manner via transfer of Eomes protein between adjacent embryonic cells. Blocking of Eomes protein transfer using a farnesylated red fluorescent protein (CherryF) also prevents Eomes nuclear accumulation. Transfer of Eomes protein between cells is mediated by the Eomes carboxyl terminus (456-692). A carbohydrate binding domain within the Eomes carboxyl-terminal region is sufficient for transfer and important for gene activation. We propose a novel mechanism by which Eomes helps effect a cellular response to a morphogen gradient.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Activins / metabolism*
  • Amino Acid Sequence
  • Animals
  • Antibodies / immunology
  • Binding Sites
  • Cell Membrane / metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Mesoderm / embryology
  • Mesoderm / metabolism
  • Molecular Sequence Data
  • Protein Binding
  • Sepharose / metabolism
  • Sequence Alignment
  • Signal Transduction*
  • Smad2 Protein / genetics
  • Smad2 Protein / metabolism*
  • T-Box Domain Proteins / chemistry
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology
  • T-Box Domain Proteins / metabolism*
  • Transforming Growth Factor beta / metabolism*
  • Xenopus Proteins / chemistry
  • Xenopus Proteins / genetics
  • Xenopus Proteins / immunology
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / embryology
  • Xenopus laevis / genetics
  • Xenopus laevis / metabolism

Substances

  • Antibodies
  • EOMES protein, Xenopus
  • Smad2 Protein
  • T-Box Domain Proteins
  • Transforming Growth Factor beta
  • Xenopus Proteins
  • Activins
  • Sepharose

Associated data

  • GENBANK/U75996