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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Regulation of nucleocytoplasmic shuttling of bruton's tyrosine kinase (Btk) through a novel sh3-dependent interaction with ankyrin repeat domain 54 (ANKRD54)
Molecular and Cellular Biology, Volume 32, No. 13, Year 2012
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Description
Bruton's tyrosine kinase (Btk), belonging to the Tec family of tyrosine kinases (TFKs), is essential for B-lymphocyte development. Abrogation of Btk signaling causes human X-linked agammaglobulinemia (XLA) and murine X-linked immunodeficiency (Xid). We employed affinity purification of Flag-tagged Btk, combined with tandem mass spectrometry, to capture and identify novel interacting proteins. We here characterize the interaction with ankryin repeat domain 54 protein (ANKRD54), also known as Lyn-interacting ankyrin repeat protein (Liar). While Btk is a nucleocytoplasmic protein, the Liar pool was found to shuttle at a higher rate than Btk. Importantly, our results suggest that Liar mediates nuclear export of both Btk and another TFK, Txk/Rlk. Liar-mediated Btk shuttling was enriched for activation loop, nonphosphorylated Btk and entirely dependent on Btk's SH3 domain. Liar also showed reduced binding to an aspartic acid phosphomimetic SH3 mutant. Three other investigated nucleus-located proteins, Abl, estrogen receptor β (ERβ), and transcription factor T-bet, were all unaffected by Liar. We mapped the interaction site to the C terminus of the Btk SH3 domain. A biotinylated, synthetic Btk peptide, ARDKNGQEGYIPSNYVTEAEDS, was sufficient for this interaction. Liar is the first protein identified that specifically influences the nucleocytoplasmic shuttling of Btk and Txk and belongs to a rare group of known proteins carrying out this activity in a Crm1-dependent manner. © 2012, American Society for Microbiology.
Authors & Co-Authors
Gustafsson, Manuela O.
Sweden, Stockholm
Karolinska Universitetssjukhuset
Hussain, Alamdar
Sweden, Stockholm
Karolinska Universitetssjukhuset
Mohammad, Dara K.
Sweden, Stockholm
Karolinska Universitetssjukhuset
Mohamed, Abdalla J.
Sweden, Stockholm
Karolinska Universitetssjukhuset
Brunei Darussalam, Bandar Seri Begawan
Universiti Brunei Darussalam
Nguyen, Vivian
Canada, Toronto
The Lunenfeld-tanenbaum Research Institute of University of Toronto
Metalnikov, Pavel
Canada, Toronto
The Lunenfeld-tanenbaum Research Institute of University of Toronto
Russian Federation, Moscow
All-russian State Centre for Quality and Standardization of Veterinary Drugs and Feed
Colwill, Karen
Canada, Toronto
The Lunenfeld-tanenbaum Research Institute of University of Toronto
Pawson, Tony J.
Canada, Toronto
The Lunenfeld-tanenbaum Research Institute of University of Toronto
Canada, Toronto
University of Toronto
Smith, Carl Inge Edvard
Sweden, Stockholm
Karolinska Universitetssjukhuset
Nore, Beston Faiek
Sweden, Stockholm
Karolinska Universitetssjukhuset
Iraq, Sulaymaniyah
University of Sulaimani
Statistics
Citations: 37
Authors: 10
Affiliations: 6
Identifiers
Doi:
10.1128/MCB.06620-11
ISSN:
02707306
e-ISSN:
10985549
Research Areas
Cancer