Functional dissection of the TBK1 molecular network.
TANK-binding kinase 1 (TBK1) and inducible IκB-kinase (IKK-i) are central regulators of type-I interferon induction. They are associated with three adaptor proteins called TANK, Sintbad (or TBKBP1) and NAP1 (or TBKBP2, AZI2) whose functional relationship to TBK1 and IKK-i is poorly understood. We pe...
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2011
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oai:doaj.org-article:e9c41f2b34d943d494a88ae43a55720f2021-11-04T06:09:05ZFunctional dissection of the TBK1 molecular network.1932-620310.1371/journal.pone.0023971https://doaj.org/article/e9c41f2b34d943d494a88ae43a55720f2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21931631/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203TANK-binding kinase 1 (TBK1) and inducible IκB-kinase (IKK-i) are central regulators of type-I interferon induction. They are associated with three adaptor proteins called TANK, Sintbad (or TBKBP1) and NAP1 (or TBKBP2, AZI2) whose functional relationship to TBK1 and IKK-i is poorly understood. We performed a systematic affinity purification-mass spectrometry approach to derive a comprehensive TBK1/IKK-i molecular network. The most salient feature of the network is the mutual exclusive interaction of the adaptors with the kinases, suggesting distinct alternative complexes. Immunofluorescence data indicated that the individual adaptors reside in different subcellular locations. TANK, Sintbad and NAP1 competed for binding of TBK1. The binding site for all three adaptors was mapped to the C-terminal coiled-coil 2 region of TBK1. Point mutants that affect binding of individual adaptors were used to reconstitute TBK1/IKK-i-deficient cells and dissect the functional relevance of the individual kinase-adaptor edges within the network. Using a microarray-derived gene expression signature of TBK1 in response virus infection or poly(I∶C) stimulation, we found that TBK1 activation was strictly dependent on the integrity of the TBK1/TANK interaction.Adriana GoncalvesTilmann BürckstümmerEvelyn DixitRuth ScheicherMaria W GórnaEvren KarayelCristina SugarAlexey StukalovTiina BergRobert KralovicsMelanie PlanyavskyKeiryn L BennettJacques ColingeGiulio Superti-FurgaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e23971 (2011) |
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| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Adriana Goncalves Tilmann Bürckstümmer Evelyn Dixit Ruth Scheicher Maria W Górna Evren Karayel Cristina Sugar Alexey Stukalov Tiina Berg Robert Kralovics Melanie Planyavsky Keiryn L Bennett Jacques Colinge Giulio Superti-Furga Functional dissection of the TBK1 molecular network. |
| description |
TANK-binding kinase 1 (TBK1) and inducible IκB-kinase (IKK-i) are central regulators of type-I interferon induction. They are associated with three adaptor proteins called TANK, Sintbad (or TBKBP1) and NAP1 (or TBKBP2, AZI2) whose functional relationship to TBK1 and IKK-i is poorly understood. We performed a systematic affinity purification-mass spectrometry approach to derive a comprehensive TBK1/IKK-i molecular network. The most salient feature of the network is the mutual exclusive interaction of the adaptors with the kinases, suggesting distinct alternative complexes. Immunofluorescence data indicated that the individual adaptors reside in different subcellular locations. TANK, Sintbad and NAP1 competed for binding of TBK1. The binding site for all three adaptors was mapped to the C-terminal coiled-coil 2 region of TBK1. Point mutants that affect binding of individual adaptors were used to reconstitute TBK1/IKK-i-deficient cells and dissect the functional relevance of the individual kinase-adaptor edges within the network. Using a microarray-derived gene expression signature of TBK1 in response virus infection or poly(I∶C) stimulation, we found that TBK1 activation was strictly dependent on the integrity of the TBK1/TANK interaction. |
| format |
article |
| author |
Adriana Goncalves Tilmann Bürckstümmer Evelyn Dixit Ruth Scheicher Maria W Górna Evren Karayel Cristina Sugar Alexey Stukalov Tiina Berg Robert Kralovics Melanie Planyavsky Keiryn L Bennett Jacques Colinge Giulio Superti-Furga |
| author_facet |
Adriana Goncalves Tilmann Bürckstümmer Evelyn Dixit Ruth Scheicher Maria W Górna Evren Karayel Cristina Sugar Alexey Stukalov Tiina Berg Robert Kralovics Melanie Planyavsky Keiryn L Bennett Jacques Colinge Giulio Superti-Furga |
| author_sort |
Adriana Goncalves |
| title |
Functional dissection of the TBK1 molecular network. |
| title_short |
Functional dissection of the TBK1 molecular network. |
| title_full |
Functional dissection of the TBK1 molecular network. |
| title_fullStr |
Functional dissection of the TBK1 molecular network. |
| title_full_unstemmed |
Functional dissection of the TBK1 molecular network. |
| title_sort |
functional dissection of the tbk1 molecular network. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/e9c41f2b34d943d494a88ae43a55720f |
| work_keys_str_mv |
AT adrianagoncalves functionaldissectionofthetbk1molecularnetwork AT tilmannburckstummer functionaldissectionofthetbk1molecularnetwork AT evelyndixit functionaldissectionofthetbk1molecularnetwork AT ruthscheicher functionaldissectionofthetbk1molecularnetwork AT mariawgorna functionaldissectionofthetbk1molecularnetwork AT evrenkarayel functionaldissectionofthetbk1molecularnetwork AT cristinasugar functionaldissectionofthetbk1molecularnetwork AT alexeystukalov functionaldissectionofthetbk1molecularnetwork AT tiinaberg functionaldissectionofthetbk1molecularnetwork AT robertkralovics functionaldissectionofthetbk1molecularnetwork AT melanieplanyavsky functionaldissectionofthetbk1molecularnetwork AT keirynlbennett functionaldissectionofthetbk1molecularnetwork AT jacquescolinge functionaldissectionofthetbk1molecularnetwork AT giuliosupertifurga functionaldissectionofthetbk1molecularnetwork |
| _version_ |
1718445184031653888 |