HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vigorito, E. Articles by Turner, M. Search for Related Content PubMed PubMed Citation Articles by Vigorito, E. Articles by Turner, M.

Vav-Dependent and Vav-Independent Phosphatidylinositol 3-Kinase Activation in Murine B Cells Determined by the Nature of the Stimulus¹

Elena Vigorito^2,*, Giuseppe Bardi^*, Janet Glassford, Eric W.-F. Lam, Elizabeth Clayton^* and Martin Turner^*

^* Laboratory of Lymphocyte Signaling and Development, Molecular Immunology Programme, Babraham Institute, Babraham, Cambridge, United Kingdom; and Cancer Research-United Kingdom Labs and Section of Cancer Cell Biology, Department of Cancer Medicine, Imperial College London, London, United Kingdom

We show in this study that B cell activation following high avidity ligation of IgM or coligation of membrane Ig with CD19 elicits similar levels of Ca²⁺ flux using different mechanisms. Each form of activation requires the function of Vav and PI3K. However, Vav regulates Ca²⁺ flux independently of PI3K following anti-IgM cross-linking. By contrast, Vav function is essential for PI3K activation following membrane Ig (mIg)/CD19 coligation. Inhibition of PI3K revealed anti-IgM-stimulated Ca²⁺ flux has a PI3K-independent component, while Ca²⁺ flux following mIg/CD19 coligation is totally PI3K dependent. The p85 and p110 subunits of PI3K both participate in anti-IgM and mIg/CD19 coligation-induced Ca²⁺ flux, although the defects are not as severe as observed after pharmacological inhibition. This may reflect the recruitment of additional PI3K subunits, as we found that p110 becomes associated with CD19 upon B cell activation. These data show that the nature of the Ag encountered by B cells determines the contribution of Vav proteins to PI3K activation. Our results indicate that the strong signals delivered by multivalent cross-linking agents activate B cells in a qualitatively different manner from those triggered by coreceptor recruitment.

This article has been cited by other articles:

				M. J. Caloca, J. L. Zugaza, and X. R. Bustelo Mechanistic Analysis of the Amplification and Diversification Events Induced by Vav Proteins in B-lymphocytes J. Biol. Chem., December 26, 2008; 283(52): 36454 - 36464. [Abstract] [Full Text] [PDF]

				M. Weber, B. Treanor, D. Depoil, H. Shinohara, N. E. Harwood, M. Hikida, T. Kurosaki, and F. D. Batista Phospholipase C-{gamma}2 and Vav cooperate within signaling microclusters to propagate B cell spreading in response to membrane-bound antigen J. Exp. Med., April 14, 2008; 205(4): 853 - 868. [Abstract] [Full Text] [PDF]

				M. L. Janas, D. Hodson, Z. Stamataki, S. Hill, K. Welch, L. Gambardella, L. C. Trotman, P. P. Pandolfi, E. Vigorito, and M. Turner The Effect of Deleting p110{delta} on the Phenotype and Function of PTEN-Deficient B Cells J. Immunol., January 15, 2008; 180(2): 739 - 746. [Abstract] [Full Text] [PDF]

				B. Wei, S. da Rocha Dias, H. Wang, and C. E. Rudd CTL-Associated Antigen-4 Ligation Induces Rapid T Cell Polarization That Depends on Phosphatidylinositol 3-Kinase, Vav-1, Cdc42, and Myosin Light Chain Kinase J. Immunol., July 1, 2007; 179(1): 400 - 408. [Abstract] [Full Text] [PDF]

				C. Charvet, A. J. Canonigo, S. Becart, U. Maurer, A. V. Miletic, W. Swat, M. Deckert, and A. Altman Vav1 Promotes T Cell Cycle Progression by Linking TCR/CD28 Costimulation to FOXO1 and p27kip1 Expression J. Immunol., October 15, 2006; 177(8): 5024 - 5031. [Abstract] [Full Text] [PDF]

				A. Bilancio, K. Okkenhaug, M. Camps, J. L. Emery, T. Ruckle, C. Rommel, and B. Vanhaesebroeck Key role of the p110{delta} isoform of PI3K in B-cell antigen and IL-4 receptor signaling: comparative analysis of genetic and pharmacologic interference with p110{delta} function in B cells Blood, January 15, 2006; 107(2): 642 - 650. [Abstract] [Full Text] [PDF]

				P. A. Madureira, P. Matos, I. Soeiro, L. K. Dixon, J. P. Simas, and E. W.-F. Lam Murine {gamma}-Herpesvirus 68 Latency Protein M2 Binds to Vav Signaling Proteins and Inhibits B-cell Receptor-induced Cell Cycle Arrest and Apoptosis in WEHI-231 B Cells J. Biol. Chem., November 11, 2005; 280(45): 37310 - 37318. [Abstract] [Full Text] [PDF]

				E. Vigorito, L. Gambardella, F. Colucci, S. McAdam, and M. Turner Vav proteins regulate peripheral B-cell survival Blood, October 1, 2005; 106(7): 2391 - 2398. [Abstract] [Full Text] [PDF]

				B. Hebeis, E. Vigorito, D. Kovesdi, and M. Turner Vav proteins are required for B-lymphocyte responses to LPS Blood, July 15, 2005; 106(2): 635 - 640. [Abstract] [Full Text] [PDF]

				V. Vedham, H. Phee, and K. M. Coggeshall Vav Activation and Function as a Rac Guanine Nucleotide Exchange Factor in Macrophage Colony-Stimulating Factor-Induced Macrophage Chemotaxis Mol. Cell. Biol., May 15, 2005; 25(10): 4211 - 4220. [Abstract] [Full Text] [PDF]