A function for AAMP in Nod2-mediated NF-kappaB activation.
The WD40 repeat containing angio-associated migratory cell protein (AAMP) was identified as a new binding partner of the human nucleotide-binding domain, leucine rich repeat containing (NLR) family member Nod2 in a yeast two-hybrid screen. Co-immunoprecipitations from human cells verified this interaction and revealed that an internal peptide of AAMP spanning three WD40 domains was sufficient for this interaction. AAMP was found to be ubiquitously expressed in different human cell-lines and exhibited a predominant cytosolic localization in epithelial cells. Functionally, using overexpression and siRNA knock-down, we showed that AAMP modulates Nod2- and Nod1-mediated NF-kappaB activation in HEK293T cells. Taken together, our data support a new function of AAMP in regulating innate immune responses initiated by the NLR protein Nod2.
Bielig
H
H
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Germany.
Zurek
B
B
Kutsch
A
A
Menning
M
M
Philpott
D J
DJ
Sansonetti
P J
PJ
Kufer
T A
TA
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D025941:Protein Interaction Mapping; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
C093492:AAMP protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D016328:NF-kappa B; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D011947:Receptors, Antigen, B-Cell; D008156:Luciferases