Mechanistic Analysis of the Amplification and Diversification Events Induced by Vav Proteins in B-lymphocytes

被引:18
作者
Caloca, Maria J.
Zugaza, Jose L.
Bustelo, Xose R. [1 ]
机构
[1] Univ Salamanca, CSIC, Ctr Invest Canc, E-37007 Salamanca, Spain
关键词
D O I
10.1074/jbc.M803814200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Vav proteins participate in the assembly of a multibranched signal transduction pathway in lymphocytes, including the stimulation of the phosphatidylinositol 3-kinase/protein kinase B and the phospholipase C-gamma/Ras GDP-releasing protein/Ras/Erk routes. In the present work, we used a genetic approach in chicken DT40 B-cell lines to investigate additional elements of the Vav route, the synergisms existing among the different Vav signaling branches, and the activities exerted by wild-type and oncogenic Vav proteins in B-lymphocytes. We show here that the Vav pathway is ramified in B-lymphocytes in additional diacylglycerol-dependent signaling branches such as those involving protein kinase C, protein kinase D, and phospholipase D. By using side-by-side comparisons of the activation levels of those signal transduction pathways in inhibitor-treated and knockout DT40 cells, we show that B-cells have different requirements regarding Vav proteins for the activation of antigen receptor downstream elements. Furthermore, we have detected interpathway cross-talk at the level of the most proximal elements but not among the most distal effector molecules of the Vav route. Finally, we show that the oncogenic versions of Vav1 and RhoA can activate alternative routes that could contribute to signal amplification and diversification events in transformed lymphocytes.
引用
收藏
页码:36454 / 36464
页数:11
相关论文
共 54 条
[1]   GEFs and GAPs: Critical elements in the control of small G proteins [J].
Bos, Johannes L. ;
Rehmann, Holger ;
Wittinghofer, Alfred .
CELL, 2007, 129 (05) :865-877
[2]   GTP-binding proteins of the Rho/Rac family: regulation, effectors and functions in vivo [J].
Bustelo, Xose R. ;
Sauzeau, Vincent ;
Berenjeno, Inmaculada M. .
BIOESSAYS, 2007, 29 (04) :356-370
[3]   Regulatory and signaling properties of the Vav family [J].
Bustelo, XR .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (05) :1461-1477
[4]   Regulation of Vav proteins by intramolecular events [J].
Bustelo, XR .
FRONTIERS IN BIOSCIENCE, 2002, 7 :D24-D30
[5]  
BUSTELO XR, 1995, MOL CELL BIOL, V15, P1324
[6]   Vav proteins, adaptors and cell signaling [J].
Bustelo, XR .
ONCOGENE, 2001, 20 (44) :6372-6381
[7]  
BUSTELO XR, 2008, UCSD NATURE MOL PAGE, DOI DOI 10.1038/MP.A002361.002301
[8]  
BUSTELO XR, 2008, UCSD NAT MOL PAGES, DOI DOI 10.1038/MP.A002362.002301
[9]   Role of chimaerins, a group of Rac-specific GTPase activating proteins, in T-cell receptor signaling [J].
Caloca, Maria Jose ;
Delgado, Pilar ;
Alarcon, Balbino ;
Bustelo, Xose R. .
CELLULAR SIGNALLING, 2008, 20 (04) :758-770
[10]   F-actin-dependent translocation of the Rap1 GDP/GTP exchange factor RasGRP2 [J].
Caloca, MJ ;
Zugaza, JL ;
Vicente-Manzanares, M ;
Sànchez-Madrid, F ;
Bustelo, XR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (19) :20435-20446