کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2167237 | 1549413 | 2012 | 8 صفحه PDF | دانلود رایگان |
B-lymphocytes produce protective antibodies but also contribute to autoimmunity. In particular, marginal zone (MZ) B cells recognize both microbial components and self-antigens. B cell trafficking is critical for B cell activation and is controlled by chemoattactants such as CXCL13 and sphingosine 1-phosphate (S1P). The related tyrosine kinases focal adhesion kinase (FAK) and proline-rich tyrosine kinase (Pyk2) regulate cell migration and adhesion but their roles in B cells are not fully understood. Using a novel Pyk2-selective inhibitor described herein (PF-719), as well as a FAK-selective inhibitor, we show that both Pyk2 and FAK are important for CXCL13- and S1P-induced migration of B-2 cells and MZ B cells. In contrast, LFA-1-mediated adhesion required only Pyk2 whereas activation of the Akt pro-survival kinase required FAK but not Pyk2. Thus Pyk2 and FAK mediate critical processes in B cells and these inhibitors can be used to further elucidate their functions in B cells.
► We synthesized a novel Pyk2-selective small molecule inhibitor, PF-719.
► Inhibitors of Pyk2 and FAK were used to probe the roles of these kinases in B cells.
► Both Pyk2 and FAK contribute to B cell migration towards CXCL13 and S1P.
► Pyk2 activity is required for B cell adhesion to ICAM-1.
► FAK activity is required for chemoattractant and BCR-induced Akt phosphorylation.
Journal: Cellular Immunology - Volume 275, Issues 1–2, January–February 2012, Pages 47–54