Document Detail

SYK regulates B-cell migration by phosphorylation of the F-actin interacting protein SWAP-70.
MedLine Citation:
PMID:  21123826     Owner:  NLM     Status:  MEDLINE    
B-cell migration into and within lymphoid tissues is not only central to the humoral immune response but also for the development of malignancies and autoimmunity. We previously demonstrated that SWAP-70, an F-actin-binding, Rho GTPase-interacting protein strongly expressed in activated B cells, is necessary for normal B-cell migration in vivo. SWAP-70 regulates integrin-mediated adhesion and cell attachment. Here we show that upon B-cell activation, SWAP-70 is extensively posttranslationally modified and becomes tyrosine phosphorylated by SYK at position 517. This phosphorylation inhibits binding of SWAP-70 to F-actin. Phospho-site mutants of SWAP-70 disrupt B-cell polarization in a dominant-negative fashion in vitro and impair migration in vivo. After CXCL12 stimulation of B cells SYK becomes activated and SWAP-70 is phosphorylated in a SYK-dependent manner. Use of the highly specific SYK inhibitor BAY61-3606 showed SYK activity is necessary for normal chemotaxis and B-cell polarization in vitro and for entry of B cells into lymph nodes in vivo. These findings demonstrate a novel requirement for SYK in migration and polarization of naive recirculating B cells and show that SWAP-70 is an important target of SYK in this pathway.
Glen Pearce; Tatsiana Audzevich; Rolf Jessberger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-12-01
Journal Detail:
Title:  Blood     Volume:  117     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-04     Completed Date:  2011-04-14     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1574-84     Citation Subset:  AIM; IM    
Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Dresden University of Technology, Fiedlerstrasse 42, Dresden, Germany.
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MeSH Terms
Actins / metabolism*
B-Lymphocytes / cytology,  metabolism*
Blotting, Western
Cell Movement*
DNA-Binding Proteins / physiology*
Flow Cytometry
Guanine Nucleotide Exchange Factors / physiology*
Intracellular Signaling Peptides and Proteins / genetics,  isolation & purification,  metabolism*
Nuclear Proteins / physiology*
Protein-Tyrosine Kinases / genetics,  isolation & purification,  metabolism*
Tyrosine / metabolism*
Reg. No./Substance:
0/Actins; 0/DNA-Binding Proteins; 0/Guanine Nucleotide Exchange Factors; 0/Intracellular Signaling Peptides and Proteins; 0/Nuclear Proteins; 0/Swap70 protein, mouse; 55520-40-6/Tyrosine; EC Kinases; EC kinase

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