Physical and functional interaction of filamin (actin-binding protein-280) and tumor necrosis factor receptor-associated factor 2.

Tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) is an intracellular protein involved in signal transduction from TNF receptor I and II and related receptors. TRAF2 is required for TNF-induced activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), and TRAF2 can also mediate activation of NF-kappaB. Here we have identified ...
the actin-binding protein Filamin (actin-binding protein-280) as a TRAF2-interacting protein. Filamin binds to the Ring zinc finger domain of TRAF2. Overexpressed Filamin inhibits TRAF2-induced activation of JNK/SAPK and of NF-kappaB. Furthermore, ectopically expressed Filamin inhibits NF-kappaB activation induced via TNF, interleukin-1, Toll receptors, and TRAF6 but not activation induced via overexpression of NIK, a downstream effector in these pathways. Importantly, TNF fails to activate SAPK or NF-kappaB in a human melanoma cell line deficient in Filamin. Reintroduction of Filamin into these cells restores the TNF response. The data imply a role for Filamin in inflammatory signal transduction pathways.
Mesh Terms:
Binding Sites, Contractile Proteins, Humans, JNK Mitogen-Activated Protein Kinases, Microfilament Proteins, Mitogen-Activated Protein Kinases, NF-kappa B, Protein Binding, Protein-Serine-Threonine Kinases, Proteins, Receptors, Cell Surface, Receptors, Immunologic, Receptors, Interleukin-1, Receptors, Tumor Necrosis Factor, Signal Transduction, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 6, Zinc Fingers
J. Biol. Chem.
Date: Jan. 07, 2000
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