Grb2 and the non-T cell activation linker NTAL constitute a Ca2+-regulating signal circuit in B lymphocytes

Stork B, Engelke M, Frey J, Horejsi V, Hamm-Baarke A, Schraven B, Kurosaki T, Wienands J (2004)
IMMUNITY 21(5): 681-691.

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Abstract
Activation of the B cell antigen receptor triggers phosphorylation of cytoplasmic and transmembrane adaptor proteins such as SLP-65 and NTAL, respectively. Specific phosphoacceptor sites in SLP-65 serve as docking sites for Ca2+-mobilizing enzymes Btk and PLC-gamma2. Phosphorylated NTAL recruits the Grb2 linker, but downstream signaling cascades are unclear. We now show that receptor-induced tyrosine phosphorylation of NTAL and concomitant Grb2 complex formation critically modulate the Ca2+ response without affecting SLP-65 and PLC-gamma2 phosphorylation. Grb2 turned out to play a negative regulatory role, which appears to be eliminated upon binding to NTAL. This allows for a sustained release of intracellular Ca2+ and is mandatory for subsequent entry of Ca2+ from extracellular sources. Thus, elevation of Ca2+ is regulated by at least two signaling modules, the B cell-specific Ca2+ initiation complex comprising SLP-65, Btk, and PLC-gamma2 and the more ubiquitously expressed NTAL/Grb2 complex, which acts as an amplifier by switching off inhibitory elements.
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Stork B, Engelke M, Frey J, et al. Grb2 and the non-T cell activation linker NTAL constitute a Ca2+-regulating signal circuit in B lymphocytes. IMMUNITY. 2004;21(5):681-691.
Stork, B., Engelke, M., Frey, J., Horejsi, V., Hamm-Baarke, A., Schraven, B., Kurosaki, T., et al. (2004). Grb2 and the non-T cell activation linker NTAL constitute a Ca2+-regulating signal circuit in B lymphocytes. IMMUNITY, 21(5), 681-691.
Stork, B., Engelke, M., Frey, J., Horejsi, V., Hamm-Baarke, A., Schraven, B., Kurosaki, T., and Wienands, J. (2004). Grb2 and the non-T cell activation linker NTAL constitute a Ca2+-regulating signal circuit in B lymphocytes. IMMUNITY 21, 681-691.
Stork, B., et al., 2004. Grb2 and the non-T cell activation linker NTAL constitute a Ca2+-regulating signal circuit in B lymphocytes. IMMUNITY, 21(5), p 681-691.
B. Stork, et al., “Grb2 and the non-T cell activation linker NTAL constitute a Ca2+-regulating signal circuit in B lymphocytes”, IMMUNITY, vol. 21, 2004, pp. 681-691.
Stork, B., Engelke, M., Frey, J., Horejsi, V., Hamm-Baarke, A., Schraven, B., Kurosaki, T., Wienands, J.: Grb2 and the non-T cell activation linker NTAL constitute a Ca2+-regulating signal circuit in B lymphocytes. IMMUNITY. 21, 681-691 (2004).
Stork, B, Engelke, M, Frey, Jürgen, Horejsi, V, Hamm-Baarke, A, Schraven, B, Kurosaki, T, and Wienands, J. “Grb2 and the non-T cell activation linker NTAL constitute a Ca2+-regulating signal circuit in B lymphocytes”. IMMUNITY 21.5 (2004): 681-691.
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Data provided by Europe PubMed Central.

IRF4 Deficiency Leads to Altered BCR Signalling Revealed by Enhanced PI3K Pathway, Decreased SHIP Expression and Defected Cytoskeletal Responses.
Budzynska PM, Niemela M, Sarapulov AV, Kylaniemi MK, Nera KP, Junttila S, Laiho A, Mattila PK, Alinikula J, Lassila O., Scand. J. Immunol. 82(5), 2015
PMID: 26173778
An integrated transcriptome and expressed variant analysis of sepsis survival and death.
Tsalik EL, Langley RJ, Dinwiddie DL, Miller NA, Yoo B, van Velkinburgh JC, Smith LD, Thiffault I, Jaehne AK, Valente AM, Henao R, Yuan X, Glickman SW, Rice BJ, McClain MT, Carin L, Corey GR, Ginsburg GS, Cairns CB, Otero RM, Fowler VG Jr, Rivers EP, Woods CW, Kingsmore SF., Genome Med 6(11), 2014
PMID: 25538794
The immunoglobulin tail tyrosine motif upgrades memory-type BCRs by incorporating a Grb2-Btk signalling module.
Engels N, Konig LM, Schulze W, Radtke D, Vanshylla K, Lutz J, Winkler TH, Nitschke L, Wienands J., Nat Commun 5(), 2014
PMID: 25413232
No receptor stands alone: IgG B-cell receptor intrinsic and extrinsic mechanisms contribute to antibody memory.
Xu Y, Xu L, Zhao M, Xu C, Fan Y, Pierce SK, Liu W., Cell Res. 24(6), 2014
PMID: 24839903
Nck-mediated recruitment of BCAP to the BCR regulates the PI(3)K-Akt pathway in B cells.
Castello A, Gaya M, Tucholski J, Oellerich T, Lu KH, Tafuri A, Pawson T, Wienands J, Engelke M, Batista FD., Nat. Immunol. 14(9), 2013
PMID: 23913047
The Dok-3/Grb2 protein signal module attenuates Lyn kinase-dependent activation of Syk kinase in B cell antigen receptor microclusters.
Losing M, Goldbeck I, Manno B, Oellerich T, Schnyder T, Bohnenberger H, Stork B, Urlaub H, Batista FD, Wienands J, Engelke M., J. Biol. Chem. 288(4), 2013
PMID: 23223229
CD22 and autoimmune disease.
Dorner T, Shock A, Smith KG., Int. Rev. Immunol. 31(5), 2012
PMID: 23083346
Epstein-Barr virus LMP2A signaling in statu nascendi mimics a B cell antigen receptor-like activation signal.
Engels N, Yigit G, Emmerich CH, Czesnik D, Schild D, Wienands J., Cell Commun. Signal 10(), 2012
PMID: 22472181
Growth-factor receptor-bound protein-2 (Grb2) signaling in B cells controls lymphoid follicle organization and germinal center reaction.
Jang IK, Cronshaw DG, Xie LK, Fang G, Zhang J, Oh H, Fu YX, Gu H, Zou Y., Proc. Natl. Acad. Sci. U.S.A. 108(19), 2011
PMID: 21508326
Fc gamma receptor IIb modulates the molecular Grb2 interaction network in activated B cells.
Neumann K, Oellerich T, Heine I, Urlaub H, Engelke M., Cell. Signal. 23(5), 2011
PMID: 21262349
A tale of two TRAPs: LAT and LAB in the regulation of lymphocyte development, activation, and autoimmunity.
Fuller DM, Zhu M, Ou-Yang CW, Sullivan SA, Zhang W., Immunol. Res. 49(1-3), 2011
PMID: 21136199
SLP-65 phosphorylation dynamics reveals a functional basis for signal integration by receptor-proximal adaptor proteins.
Oellerich T, Gronborg M, Neumann K, Hsiao HH, Urlaub H, Wienands J., Mol. Cell Proteomics 8(7), 2009
PMID: 19372136
Adaptor molecules expression in normal lymphopoiesis and in childhood leukemia.
Svojgr K, Burjanivova T, Vaskova M, Kalina T, Stary J, Trka J, Zuna J., Immunol. Lett. 122(2), 2009
PMID: 19183565
Proliferative signals mediated by CD28 superagonists require the exchange factor Vav1 but not phosphoinositide 3-kinase in primary peripheral T cells.
Gogishvili T, Elias F, Emery JL, McPherson K, Okkenhaug K, Hunig T, Dennehy KM., Eur. J. Immunol. 38(9), 2008
PMID: 18792405
Ntal/Lab/Lat2.
Iwaki S, Jensen BM, Gilfillan AM., Int. J. Biochem. Cell Biol. 39(5), 2007
PMID: 17118694
Adaptive and innate immune reactions regulating mast cell activation: from receptor-mediated signaling to responses.
Tkaczyk C, Jensen BM, Iwaki S, Gilfillan AM., Immunol Allergy Clin North Am 26(3), 2006
PMID: 16931287
The transmembrane adapter protein SIT regulates thymic development and peripheral T-cell functions.
Simeoni L, Posevitz V, Kolsch U, Meinert I, Bruyns E, Pfeffer K, Reinhold D, Schraven B., Mol. Cell. Biol. 25(17), 2005
PMID: 16107703
Expression and function of the adaptor protein Gads in murine B cells.
Yankee TM, Draves KE, Clark EA., Eur. J. Immunol. 35(4), 2005
PMID: 15761845

45 References

Data provided by Europe PubMed Central.

Adapters in lymphocyte signaling.
Leo A, Wienands J, Baier G, Horejsi V, Schraven B., J. Clin. Invest. 109(3), 2002
PMID: 11827988
Transient receptor potential 1 regulates capacitative Ca(2+) entry and Ca(2+) release from endoplasmic reticulum in B lymphocytes.
Mori Y, Wakamori M, Miyakawa T, Hermosura M, Hara Y, Nishida M, Hirose K, Mizushima A, Kurosaki M, Mori E, Gotoh K, Okada T, Fleig A, Penner R, Iino M, Kurosaki T., J. Exp. Med. 195(6), 2002
PMID: 11901194
Plat-E: an efficient and stable system for transient packaging of retroviruses.
Morita S, Kojima T, Kitamura T., Gene Ther. 7(12), 2000
PMID: 10871756
Requirement for Ras guanine nucleotide releasing protein 3 in coupling phospholipase C-gamma2 to Ras in B cell receptor signaling.
Oh-hora M, Johmura S, Hashimoto A, Hikida M, Kurosaki T., J. Exp. Med. 198(12), 2003
PMID: 14676298
Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling.
Ono M, Okada H, Bolland S, Yanagi S, Kurosaki T, Ravetch JV., Cell 90(2), 1997
PMID: 9244303
Store depletion and calcium influx.
Parekh AB, Penner R., Physiol. Rev. 77(4), 1997
PMID: 9354808
Cross-reactive idiotypes and common antigen binding specificities expressed by a series of murine B-cell lymphomas: etiological implications.
Pennell CA, Arnold LW, Lutz PM, LoCascio NJ, Willoughby PB, Haughton G., Proc. Natl. Acad. Sci. U.S.A. 82(11), 1985
PMID: 2582425
A growing family of guanine nucleotide exchange factors is responsible for activation of Ras-family GTPases.
Quilliam LA, Rebhun JF, Castro AF., Prog. Nucleic Acid Res. Mol. Biol. 71(), 2002
PMID: 12102558
Lipid rafts and signal transduction.
Simons K, Toomre D., Nat. Rev. Mol. Cell Biol. 1(1), 2000
PMID: 11413487
Interaction of SLP adaptors with the SH2 domain of Tec family kinases.
Su YW, Zhang Y, Schweikert J, Koretzky GA, Reth M, Wienands J., Eur. J. Immunol. 29(11), 1999
PMID: 10556826
Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled Ca2+ mobilization through distinct pathways.
Takata M, Sabe H, Hata A, Inazu T, Homma Y, Nukada T, Yamamura H, Kurosaki T., EMBO J. 13(6), 1994
PMID: 8137818
NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and Fc epsilon RI aggregation.
Tkaczyk C, Horejsi V, Iwaki S, Draber P, Samelson LE, Satterthwaite AB, Nahm DH, Metcalfe DD, Gilfillan AM., Blood 104(1), 2004
PMID: 15010370
Functional analysis of human Fc gamma RII (CD32) isoforms expressed in B lymphocytes.
Van Den Herik-Oudijk IE, Westerdaal NA, Henriquez NV, Capel PJ, Van De Winkel JG., J. Immunol. 152(2), 1994
PMID: 8283039
Negative regulation of immunoreceptor signaling.
Veillette A, Latour S, Davidson D., Annu. Rev. Immunol. 20(), 2002
PMID: 11861615
SLP-65: a new signaling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation.
Wienands J, Schweikert J, Wollscheid B, Jumaa H, Nielsen PJ, Reth M., J. Exp. Med. 188(4), 1998
PMID: 9705962
The role of membrane-associated adaptors in T cell receptor signalling.
Zhang W, Samelson LE., Semin. Immunol. 12(1), 2000
PMID: 10723796
LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation.
Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE., Cell 92(1), 1998
PMID: 9489702

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