The ectodermal dysplasia receptor activates the nuclear factor-kappaB, JNK, and cell death pathways and binds to ectodysplasin A.

Abstract

The ectodermal dysplasia receptor (EDAR) is a recently isolated member of the tumor necrosis factor receptor family that has been shown to play a key role in the process of ectodermal differentiation. We present evidence that EDAR is capable of activating the nuclear factor-kappaB, JNK, and caspase-independent cell death pathways and that these activities are impaired in mutants lacking its death domain or those associated with anhidrotic ectodermal dysplasia and the downless phenotype. Although EDAR possesses a death domain, it did not interact with the death domain-containing adaptor proteins TRADD and FADD. EDAR successfully interacted with various TRAF family members; however, a dominant-negative mutant of TRAF2 was incapable of blocking EDAR-induced nuclear factor-kappaB or JNK activation. Collectively, the above results suggest that EDAR utilizes a novel signal transduction pathway. Finally, ectodysplasin A can physically interact with the extracellular domain of EDAR and thus represents its biological ligand.

• Authors: A Kumar, M T Eby, S Sinha, A Jasmin, P M Chaudhary
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 4 Pg. 2668-77 (Jan 26 2001) ISSN: 0021-9258 [Print] United States
• PMID: 11035039 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ectodysplasins
• Membrane Proteins
• NF-kappa B
• Receptors, Tumor Necrosis Factor
• Protein Serine-Threonine Kinases
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinases
• NF-kappa B kinase

Topics

• Cell Death
• Ectodermal Dysplasia
• Ectodysplasins
• Enzyme Activation
• JNK Mitogen-Activated Protein Kinases
• Membrane Proteins (metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Mutagenesis
• NF-kappa B (metabolism)
• Protein Binding
• Protein Serine-Threonine Kinases (metabolism)
• Receptors, Tumor Necrosis Factor (genetics, metabolism)
• Signal Transduction