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Cutting Edge |
,
Departments of
*
Biomolecular Chemistry,
Medicine, and
Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, WI 53706;
Department of Medicine, Boston University Medical Center, Boston, MA 02118; and
¶ Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
The nucleotide receptor P2X7 has been shown to
modulate LPS-induced macrophage production of numerous inflammatory
mediators. Although the C-terminal portion of P2X7 is
thought to be essential for multiple receptor functions, little is
known regarding the structural motifs that lie within this region. We
show here that the P2X7 C-terminal domain contains several
apparent protein-protein and protein-lipid interaction motifs with
potential importance to macrophage signaling and LPS action.
Surprisingly, P2X7 also contains a conserved LPS-binding
domain. In this report, we demonstrate that peptides derived from this
P2X7 sequence bind LPS in vitro. Moreover, these peptides
neutralize the ability of LPS to activate the extracellular
signal-regulated kinases (ERK1, ERK2) and to promote the degradation of
the inhibitor of 
B-
isoform (IB-) in RAW 264.7 macrophages.
Collectively, these data suggest that the C-terminal domain of
P2X7 may directly coordinate several signal transduction
events related to macrophage function and LPS
action.
This article has been cited by other articles:
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Z. A. Pfeiffer, M. Aga, U. Prabhu, J. J. Watters, D. J. Hall, and P. J. Bertics The nucleotide receptor P2X7 mediates actin reorganization and membrane blebbing in RAW 264.7 macrophages via p38 MAP kinase and Rho J. Leukoc. Biol., June 1, 2004; 75(6): 1173 - 1182. [Abstract] [Full Text] [PDF]
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M. L. Smart, B. Gu, R. G. Panchal, J. Wiley, B. Cromer, D. A. Williams, and S. Petrou P2X7 Receptor Cell Surface Expression and Cytolytic Pore Formation Are Regulated by a Distal C-terminal Region J. Biol. Chem., February 28, 2003; 278(10): 8853 - 8860. [Abstract] [Full Text] [PDF]
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R. A. Le Feuvre, D. Brough, Y. Iwakura, K. Takeda, and N. J. Rothwell Priming of Macrophages with Lipopolysaccharide Potentiates P2X7-mediated Cell Death via a Caspase-1-dependent Mechanism, Independently of Cytokine Production J. Biol. Chem., January 25, 2002; 277(5): 3210 - 3218. [Abstract] [Full Text] [PDF]
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