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We show here that Vav-2 is tyrosine phosphorylated following antigen receptor engagement in both B- and T-cells, but potentiates nuclear factor of activated T cells (NFAT)-dependent transcription only in B cells. Vav-2 function requires the N-terminus, as well as functional Dbl homology and SH2 domains. More over, the enhancement of NFAT-dependent transcription by Vav-2 can be inhibited by a number of dominant-negative GTPases. The ability of Vav-2 to potentiate NFAT-dependent transcription correlates with its ability to promote a sustained calcium flux. Thus, Vav-2 augments the calcium signal in B cells but not T cells, and a truncated form of Vav-2 can neither activate NFAT nor augment calcium signaling. The CD19 co-receptor physically interacts with Vav-2 and synergistically enhances Vav-2 phosphorylation induced by the B-cell receptor (BCR). In addition, we found that Vav-2 augments CD19-stimulated NFAT- dependent transcription, as well as transcription from the CD5 enhancer. These data suggest a role for Vav-2 in transducing BCR signals to the transcription factor NFAT and implicate Vav-2 in the integration of BCR and CD19 signaling.

Titel:	Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes.
Autor/in / Beteiligte Person:	Doody, GM ; Billadeau, DD ; Clayton, E ; Hutchings, A ; Berland, R ; McAdam, S ; Leibson, PJ ; Turner, M
Link:	Full Text Finder (Volltext)
Zeitschrift:	The EMBO journal, Jg. 19 (2000-11-15), Heft 22, S. 6173-84
Veröffentlichung:	2024- : [London] : Nature Publishing Group ; <i>Original Publication</i>: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-, 2000
Medientyp:	academicJournal
ISSN:	0261-4189 (print)
DOI:	10.1093/emboj/19.22.6173
Schlagwort:	Animals Antigens, CD19 chemistry Antigens, CD19 metabolism B-Lymphocytes immunology CD5 Antigens genetics CD5 Antigens metabolism Cells, Cultured Humans Jurkat Cells Mice NFATC Transcription Factors Phosphorylation Proto-Oncogene Proteins c-vav Receptor Protein-Tyrosine Kinases metabolism Receptors, Antigen, B-Cell metabolism Signal Transduction T-Lymphocytes immunology Transcription, Genetic Tyrosine chemistry B-Lymphocytes metabolism DNA-Binding Proteins genetics DNA-Binding Proteins metabolism Nuclear Proteins Oncogene Proteins genetics Oncogene Proteins metabolism T-Lymphocytes metabolism Transcription Factors genetics Transcription Factors metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Language: English [EMBO J] 2000 Nov 15; Vol. 19 (22), pp. 6173-84. MeSH Terms: Nuclear Proteins* ; B-Lymphocytes / metabolism ; DNA-Binding Proteins / genetics ; DNA-Binding Proteins / metabolism ; Oncogene Proteins / genetics ; Oncogene Proteins / metabolism ; T-Lymphocytes / metabolism ; Transcription Factors / genetics ; Transcription Factors / metabolism ; Animals ; Antigens, CD19 / chemistry ; Antigens, CD19 / metabolism ; B-Lymphocytes / immunology ; CD5 Antigens / genetics ; CD5 Antigens / metabolism ; Cells, Cultured ; Humans ; Jurkat Cells ; Mice ; NFATC Transcription Factors ; Phosphorylation ; Proto-Oncogene Proteins c-vav ; Receptor Protein-Tyrosine Kinases / metabolism ; Receptors, Antigen, B-Cell / metabolism ; Signal Transduction ; T-Lymphocytes / immunology ; Transcription, Genetic ; Tyrosine / chemistry References: J Biol Chem. 2000 Jan 21;275(3):2185-90. (PMID: 10636924) ; Mol Cell Biol. 2000 Mar;20(5):1461-77. (PMID: 10669724) ; Mol Cell Biol. 2000 Mar;20(5):1678-91. (PMID: 10669745) ; Cell. 1999 Mar 5;96(5):611-4. (PMID: 10089876) ; J Immunol. 1999 Apr 15;162(8):4438-46. (PMID: 10201980) ; Curr Opin Immunol. 1999 Apr;11(2):143-51. (PMID: 10322153) ; J Immunol. 1999 Jun 15;162(12):7088-94. (PMID: 10358152) ; Curr Opin Immunol. 1999 Jun;11(3):242-8. (PMID: 10375551) ; Immunity. 1999 Aug;11(2):191-200. (PMID: 10485654) ; J Biol Chem. 1999 Oct 22;274(43):30410-8. (PMID: 10521418) ; J Immunol. 2000 Apr 15;164(8):3971-81. (PMID: 10754287) ; J Exp Med. 2000 Aug 7;192(3):381-92. (PMID: 10934226) ; Mol Cell Biol. 1991 Apr;11(4):1912-20. (PMID: 2005887) ; Nature. 1992 Mar 5;356(6364):68-71. (PMID: 1311423) ; Nature. 1992 Mar 5;356(6364):71-4. (PMID: 1531699) ; Science. 1992 May 22;256(5060):1196-9. (PMID: 1375396) ; Mol Cell Biol. 1992 Jul;12(7):3138-48. (PMID: 1620121) ; J Biol Chem. 1994 Dec 23;269(51):32514-21. (PMID: 7528218) ; Immunity. 1994 Jun;1(3):179-87. (PMID: 7889406) ; Immunity. 1994 Jun;1(3):189-96. (PMID: 7889407) ; Int Immunol. 1995 Mar;7(3):381-92. (PMID: 7540861) ; Cell. 1995 Jun 30;81(7):1159-70. (PMID: 7600583) ; Mol Cell Biol. 1995 Aug;15(8):4337-46. (PMID: 7623828) ; Science. 1995 Jul 28;269(5223):535-7. (PMID: 7542801) ; Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9810-4. (PMID: 7568223) ; Science. 1996 Jan 19;271(5247):348-50. (PMID: 8553069) ; Oncogene. 1996 Jul 18;13(2):363-71. (PMID: 8710375) ; Mol Cell Biol. 1996 Oct;16(10):5232-44. (PMID: 8816436) ; Science. 1996 Dec 13;274(5294):1906-9. (PMID: 8943203) ; Nature. 1997 Jan 9;385(6612):169-72. (PMID: 8990121) ; Mol Cell Biol. 1997 Mar;17(3):1346-53. (PMID: 9032261) ; Nature. 1997 Apr 24;386(6627):855-8. (PMID: 9126747) ; J Immunol. 1997 May 15;158(10):4662-9. (PMID: 9144478) ; Mol Cell Biol. 1997 Aug;17(8):4305-11. (PMID: 9234687) ; Immunity. 1997 Jul;7(1):59-67. (PMID: 9252120) ; Genes Dev. 1997 Sep 15;11(18):2295-322. (PMID: 9308960) ; Immunity. 1997 Oct;7(4):451-60. (PMID: 9354466) ; Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13158-62. (PMID: 9371816) ; Science. 1998 Jan 23;279(5350):558-60. (PMID: 9438848) ; J Biol Chem. 1998 May 1;273(18):11248-56. (PMID: 9556616) ; Nature. 1998 Apr 30;392(6679):933-6. (PMID: 9582075) ; Curr Biol. 1998 May 7;8(10):554-62. (PMID: 9601639) ; Curr Biol. 1998 May 7;8(10):563-72. (PMID: 9601640) ; Eur J Immunol. 1998 May;28(5):1467-80. (PMID: 9603451) ; Immunity. 1998 May;8(5):635-45. (PMID: 9620684) ; J Immunol. 1998 Jul 1;161(1):277-85. (PMID: 9647234) ; Semin Immunol. 1998 Aug;10(4):317-27. (PMID: 9695188) ; EMBO J. 1998 Oct 1;17(19):5647-57. (PMID: 9755165) ; Cell. 1998 Oct 16;95(2):259-68. (PMID: 9790532) ; EMBO J. 1998 Nov 16;17(22):6608-21. (PMID: 9822605) ; Nat Struct Biol. 1998 Dec;5(12):1098-107. (PMID: 9846881) ; Eur J Immunol. 1999 Feb;29(2):477-87. (PMID: 10064063) ; Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3035-40. (PMID: 10077632) Grant Information: R01 CA047752 United States CA NCI NIH HHS; AI15803 United States AI NIAID NIH HHS; CA47752 United States CA NCI NIH HHS Substance Nomenclature: 0 (Antigens, CD19) ; 0 (CD5 Antigens) ; 0 (DNA-Binding Proteins) ; 0 (NFATC Transcription Factors) ; 0 (Nuclear Proteins) ; 0 (Oncogene Proteins) ; 0 (Proto-Oncogene Proteins c-vav) ; 0 (Receptors, Antigen, B-Cell) ; 0 (Transcription Factors) ; 0 (VAV2 protein, human) ; 0 (Vav2 protein, mouse) ; 42HK56048U (Tyrosine) ; EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) Entry Date(s): Date Created: 20001118 Date Completed: 20010104 Latest Revision: 20181113 Update Code: 20231215 PubMed Central ID: PMC305817

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Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes.