Characterization of a cascade of protein interactions initiated at the IL-1 receptor.
Prior studies have identified molecules involved in IL-1 signaling that transmit the extracellular stimulus to downstream kinase molecules causing altered transcriptional activity. Many of these investigations have relied heavily on ligand induced protein-protein interactions detected by immuno-coprecipitation to map the cascade of events from receptor binding to activation of downstream signaling intermediates. Direct protein interactions have not been commonly reported. An in vitro study was undertaken to better define the direct protein-protein interactions involved in IL-1 signaling. Results indicate that IRAK2 is capable of direct association with either IL-1R(I) or IL-1R(AcP). IRAK2 is also capable of associating directly with MyD88 by distinct regions. Finally, IRAK2 interactions with TRAF6 were mapped and demonstrate differences from more proximal signaling intermediates. A model is presented that reflects the specific molecular interactions responsible for recruiting signaling intermediates to the IL-1 receptor cytoplasmic domains.
Boch
Jason A
JA
Department of Medicine, Harvard Medical School, and the Beth Israel Deaconess Medical Center, Boston, MA, USA.
Yoshida
Yasuhiro
Y
Koyama
Yoshinobu
Y
Wara-Aswapati
Nawarat
N
Peng
Hiabing
H
Unlu
Sebnem
S
Auron
Philip E
PE
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases; D008322:Mammals; D008958:Models, Molecular; D053594:Myeloid Differentiation Factor 88; D011487:Protein Conformation; D011494:Protein Kinases / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases