The Rap GTPases mediate CXCL13- and sphingosine1-phosphate-induced chemotaxis, adhesion, and Pyk2 tyrosine phosphorylation in B lymphocytes
✍ Scribed by Caylib A. Durand; Jens Westendorf; Kathy W. K. Tse; Michael R. Gold
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 500 KB
- Volume
- 36
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
The localization of B cells to lymphoid organs where they can become activated and differentiate into antibody‐secreting plasma cells is controlled by multiple chemoattractants that promote cell migration and integrin‐mediated adhesion. CXCL13 and sphingosine 1‐phosphate (S1P) are two important chemoattractants that control the trafficking of B cells. CXCL13 directs B lymphocytes to lymphoid follicles where they receive survival signals and, if activated, undergo a germinal center response. In contrast, S1P allows B cells and plasma cells to exit lymphoid organs and re‐enter the circulation. The Rap1 GTPase is a key regulator of cell adhesion and cell migration in a number of systems. We now show that Rap activation is required for CXCL13 and S1P to induce B cell migration as well as adhesion to ICAM‐1 and VCAM‐1. We also show that Pyk2, a tyrosine kinase involved in cytoskeleton rearrangements and B cell migration, is a downstream target of both CXCL13 and S1P signaling and that Rap activation is important for CXCL13 and S1P to stimulate tyrosine phosphorylation of Pyk2, a modification that increases Pyk2 kinase activity. This suggests that the ability of CXCL13 and S1P to direct the trafficking and localization of B cells in vivo may be dependent on Rap activation.