| SYK regulates B-cell migration by phosphorylation of the F-actin interacting protein SWAP-70. | |
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MedLine Citation:
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PMID: 21123826 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Glen Pearce; Tatsiana Audzevich; Rolf Jessberger |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-12-01 |
Journal Detail:
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Title: Blood Volume: 117 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-04 Completed Date: 2011-04-14 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 1574-84 Citation Subset: AIM; IM |
Affiliation:
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Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Dresden University of Technology, Fiedlerstrasse 42, Dresden, Germany. 6305glen.pearce@mailbox.tu-dresden.de |
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| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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metabolism* Animals B-Lymphocytes / cytology, metabolism* Blotting, Western Cell Movement* DNA-Binding Proteins / physiology* Flow Cytometry Guanine Nucleotide Exchange Factors / physiology* Immunoprecipitation Intracellular Signaling Peptides and Proteins / genetics, isolation & purification, metabolism* Mice Nuclear Proteins / physiology* Phosphorylation Protein-Tyrosine Kinases / genetics, isolation & purification, metabolism* Tyrosine / metabolism* |
| Chemical | |
Reg. No./Substance:
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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 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Syk kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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