Vav family proteins constitute disparate branching points for distinct BCR signaling pathways.

European Journal of Immunology
Jens LöberNiklas Engels

Abstract

Antigen recognition by B-cell antigen receptors (BCRs) activates distinct intracellular signaling pathways that control the differentiation fate of activated B lymphocytes. BCR-proximal signaling enzymes comprise protein tyrosine kinases, phosphatases, and plasma membrane lipid-modifying enzymes, whose function is furthermore coordinated by catalytically inert adaptor proteins. Here, we show that an additional class of enzymatic activity provided by guanine-nucleotide exchange factors (GEFs) of the Vav family controls BCR-proximal Ca2+ mobilization, cytoskeletal actin reorganization, and activation of the PI3 kinase/Akt pathway. Whereas Vav1 and Vav3 supported all of those signaling processes to different extents in a human B-cell model system, Vav2 facilitated Actin remodeling, and activation of Akt but did not promote Ca2+ signaling. On BCR activation, Vav1 was directly recruited to the phosphorylated BCR and to the central adaptor protein SLP65 via its Src homology 2 domain. Pharmacological inhibition or genetic inactivation of the substrates of Vav GEFs, small G proteins of the Rho/Rac family, impaired BCR-induced Ca2+ mobilization, probably because phospholipase Cγ2 requires activated Rac proteins for optimal activity. Our...Continue Reading

References

Mar 30, 1989·Nature·M Reth
Aug 11, 1998·Immunity·C FuA C Chan
Nov 11, 1999·European Journal of Immunology·Y W SuJ Wienands
Nov 18, 2000·The EMBO Journal·G M DoodyM Turner
Jan 24, 2002·The Journal of Experimental Medicine·Kazunori InabeTomohiro Kurosaki
Sep 14, 2002·The Journal of Biological Chemistry·José L ZugazaXosé R Bustelo
Nov 28, 2002·Molecular Cell·Véronique RolliMichael Reth
Nov 29, 2002·The EMBO Journal·Christopher W ChiuAndrew C Chan
Jul 4, 2003·The EMBO Journal·María J CalocaXosé R Bustelo
Oct 18, 2003·Science·Marita J WalmsleyVictor L J Tybulewicz
Jan 25, 2005·Molecular Cell·Abdelhafid Saci, Christopher L Carpenter
May 12, 2005·Current Opinion in Immunology·Victor L J Tybulewicz
Sep 21, 2005·The Journal of Biological Chemistry·Thomas PiechulekPeter Gierschik
Jul 13, 2007·Immunological Reviews·Michael EngelkeJürgen Wienands
Sep 15, 2007·Nature Reviews. Immunology·Andrew M ScharenbergDavid J Rawlings
May 20, 2008·Nature Structural & Molecular Biology·Pilong LiMichael K Rosen
May 31, 2008·EMBO Reports·Jonathan RapleyKatrin Rittinger
Jul 1, 2008·Journal of Molecular Biology·Jill E ChrencikPeter Kuhn
Aug 23, 2008·Nature Reviews. Molecular Cell Biology·Sarah J Heasman, Anne J Ridley
Aug 30, 2008·The Journal of Biological Chemistry·Claudia WalliserTom D Bunney
Dec 17, 2009·Science Signaling·Alexander SavelievVictor L J Tybulewicz
Mar 3, 2010·Annual Review of Immunology·Naomi E Harwood, Facundo D Batista
Oct 12, 2010·Nature Reviews. Immunology·Susan K Pierce, Wanli Liu
Aug 9, 2011·The EMBO Journal·Thomas OellerichJürgen Wienands
Mar 3, 2012·The Journal of Biological Chemistry·Brenda L Montalvo-OrtizSuranganie Dharmawardhane
Mar 8, 2012·Infectious Disorders Drug Targets·Takeshi Tsubata
Apr 5, 2012·Cell Communication and Signaling : CCS·Niklas EngelsJürgen Wienands
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Dec 31, 2014·The Journal of Experimental Medicine·Marianne BurbageFacundo D Batista
Apr 24, 2015·The Journal of Biological Chemistry·Claudia WalliserPeter Gierschik
May 4, 2017·Proceedings of the National Academy of Sciences of the United States of America·Martin BeckerPalash C Maity
Jul 24, 2018·Molecular Immunology·Katelyn M Spillane, Pavel Tolar
Apr 27, 2019·Annual Review of Immunology·Michael R Gold, Michael G Reth

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