SYK regulates B-cell migration by phosphorylation of the F-actin interacting protein SWAP-70

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

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.

Details

Original languageEnglish
Pages (from-to)1574-84
Number of pages11
JournalBlood
Volume117
Issue number5
Publication statusPublished - 3 Feb 2011
Peer-reviewedYes

External IDs

PubMed 21123826
Scopus 79551634518

Keywords

Keywords

  • Actins/metabolism, Animals, B-Lymphocytes/cytology, Blotting, Western, Cell Movement, DNA-Binding Proteins/physiology, Flow Cytometry, Guanine Nucleotide Exchange Factors/physiology, Immunoprecipitation, Intracellular Signaling Peptides and Proteins/genetics, Mice, Minor Histocompatibility Antigens, Nuclear Proteins/physiology, Phosphorylation, Protein-Tyrosine Kinases/genetics, Syk Kinase, Tyrosine/metabolism