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Genetic and physica...
Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK
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Castillejo-Lopez, Casimiro (author)
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- Delgado-Vega, Angélica M. (author)
- Uppsala universitet,Genomik
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Wojcik, Jerome (author)
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- Kozyrev, Sergey V. (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Thavathiru, Elangovan (author)
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Wu, Ying-Yu (author)
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Sanchez, Elena (author)
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- Pöllmann, David (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Lopez-Egido, Juan R. (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Fineschi, Serena (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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Dominguez, Nicolas (author)
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Lu, Rufei (author)
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James, Judith A. (author)
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Merrill, Joan T. (author)
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Kelly, Jennifer A. (author)
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Kaufman, Kenneth M. (author)
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Moser, Kathy L. (author)
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Gilkeson, Gary (author)
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- Frostegård, Johan (author)
- Karolinska Institutet
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Pons-Estel, Bernardo A. (author)
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D'Alfonso, Sandra (author)
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Witte, Torsten (author)
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Luis Callejas, Jose (author)
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Harley, John B. (author)
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Gaffney, Patrick M. (author)
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Martin, Javier (author)
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Guthridge, Joel M. (author)
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Alarcon-Riquelme, Marta E. (author)
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(creator_code:org_t)
- 2011-10-06
- 2012
- English.
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 71:1, s. 136-142
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Abstract
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- ObjectivesAltered signalling in B cells is a predominant feature of systemic lupus erythematosus (SLE). The genes BANK1 and BLK were recently described as associated with SLE. BANK1 codes for a B-cell-specific cytoplasmic protein involved in B-cell receptor signalling and BLK codes for an Src tyrosine kinase with important roles in B-cell development. To characterise the role of BANK1 and BLK in SLE, a genetic interaction analysis was performed hypothesising that genetic interactions could reveal functional pathways relevant to disease pathogenesis.MethodsThe GPAT16 method was used to analyse the gene-gene interactions of BANK1 and BLK. Confocal microscopy was used to investigate co-localisation, and immunoprecipitation was used to verify the physical interaction of BANK1 and BLK.ResultsEpistatic interactions between BANK1 and BLK polymorphisms associated with SLE were observed in a discovery set of 279 patients and 515 controls from northern Europe. A meta-analysis with 4399 European individuals confirmed the genetic interactions between BANK1 and BLK. As BANK1 was identified as a binding partner of the Src tyrosine kinase LYN, the possibility that BANK1 and BLK could also show a protein-protein interaction was tested. The co-immunoprecipitation and co-localisation of BLK and BANK1 were demonstrated. In a Daudi cell line and primary naive B cells endogenous binding was enhanced upon B-cell receptor stimulation using anti-IgM antibodies.ConclusionsThis study shows a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically. The results have important consequences for the understanding of SLE and other autoimmune diseases and identify a potential new signalling pathway.
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Castillejo-Lopez ...
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Delgado-Vega, An ...
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Wojcik, Jerome
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Kozyrev, Sergey ...
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Thavathiru, Elan ...
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Wu, Ying-Yu
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show more...
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Sanchez, Elena
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Pöllmann, David
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Lopez-Egido, Jua ...
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Fineschi, Serena
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Dominguez, Nicol ...
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Lu, Rufei
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James, Judith A.
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Merrill, Joan T.
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Kelly, Jennifer ...
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Kaufman, Kenneth ...
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Moser, Kathy L.
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Gilkeson, Gary
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Frostegård, Joha ...
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Pons-Estel, Bern ...
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D'Alfonso, Sandr ...
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Witte, Torsten
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Luis Callejas, J ...
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Harley, John B.
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Gaffney, Patrick ...
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Martin, Javier
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Guthridge, Joel ...
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Alarcon-Riquelme ...
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show less...
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Annals of the Rh ...
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Uppsala University
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Karolinska Institutet