Characterization of a novel interaction between transcription factor TFII-I and the inducible tyrosine kinase in T cells.
TCR signaling leads to the activation of kinases such as inducible tyrosine kinase (Itk), a key regulatory protein in T-lymphocyte activation and function. The homolog of Itk in B cells is Bruton's tyrosine kinase, previously shown to bind and phosphorylate the transcription factor TFII-I. TFII-I plays major roles in transcription and signaling. Our purpose herein was twofold: first, to identify some of the molecular determinants involved in TFII-I activation downstream of receptor crosslinking in T cells and second, to uncover the existence of Itk-TFII-I signaling in T lymphocytes. We report for the first time that TFII-I is tyrosine phosphorylated upon TCR, TCR/CD43, and TCR/CD28 co-receptor engagement in human and/or murine T cells. We show that Itk physically interacts with TFII-I and potentiates TFII-I-driven c-fos transcription. We demonstrate that TFII-I is phosphorylated upon co-expression of WT, but not kinase-dead, or kinase-dead/R29C mutant Itk, suggesting these residues are important for TFII-I phosphorylation, presumably via an Itk-dependent mechanism. Structural analysis of TFII-I-Itk interactions revealed that the first 90 residues of TFII-I are dispensable for Itk binding. Mutations within Itk's kinase, pleckstrin-homology, and proline-rich regions did not abolish TFII-I-Itk binding. Our results provide an initial step in understanding the biological role of Itk-TFII-I signaling in T-cell function.
Sacristán
Catarina
C
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Mexico. catarina.sacristan@med.nyu.edu
Schattgen
Stefan A
SA
Berg
Leslie J
LJ
Bunnell
Stephen C
SC
Roy
Ananda L
AL
Rosenstein
Yvonne
Y
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D016762:Genes, fos / Q000235:genetics / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D051917:Leukosialin / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019473:Transcription Factors, TFII / Q000378:metabolism*
D018106:CD28 Antigens; D017252:CD3 Complex; C104259:GTF2I protein, human; D051917:Leukosialin; C465014:SPN protein, human; D019473:Transcription Factors, TFII; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase
Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):604-9
9012831
J Immunol. 2008 Mar 1;180(5):3007-18
18292523
Mol Cell Biol. 1998 Jun;18(6):3310-20
9584171
J Biol Chem. 1986 Jun 5;261(16):7526-30
3711098
J Biol Chem. 2000 Aug 25;275(34):26300-8
10854432
Mol Cell Biol. 1998 Aug;18(8):4444-54
9671454
Cell. 1993 Jan 29;72(2):279-90
8425221
Annu Rev Immunol. 2005;23:549-600
15771581
J Biol Chem. 1996 Nov 1;271(44):27564-8
8910342
Nat Rev Immunol. 2003 Dec;3(12):939-51
14647476
Nucleic Acids Res. 1990 Sep 11;18(17):5322
1698283
Immunol Cell Biol. 2001 Jun;79(3):303-7
11380685
Nat Rev Immunol. 2007 Jun;7(6):479-85
17479128
Nature. 1993 Jan 21;361(6409):226-33
8380905
Science. 2006 Oct 6;314(5796):122-5
17023658
EMBO J. 1991 Apr;10(4):893-902
1706994
Science. 1993 Jul 16;261(5119):355-8
8332900
Nature. 1993 Sep 23;365(6444):359-61
8377829
J Biol Chem. 2004 Feb 20;279(8):7147-58
14623887
J Biol Chem. 2001 Nov 2;276(44):41435-43
11527964
J Biol Chem. 1998 Dec 11;273(50):33443-8
9837922
J Biol Chem. 1997 Oct 3;272(40):25401-8
9312162
J Biol Chem. 1998 Jun 5;273(23):14218-24
9603925
J Virol. 2005 Apr;79(7):4396-406
15767439
Mol Cell Biol. 2001 May;21(10):3387-97
11313464
Mol Cell Biol. 1999 Jul;19(7):5014-24
10373551
J Biol Chem. 2000 Oct 6;275(40):31460-8
10908570
J Immunol. 2007 Mar 1;178(5):2631-5
17312101
J Biol Chem. 2001 Mar 16;276(11):8377-83
11113127
Eur J Cancer. 2005 Nov;41(16):2528-36
16223582
Genes Cells. 2006 Apr;11(4):373-81
16611241
Virus Genes. 2007 Oct;35(2):215-23
17546494
Nature. 1991 Nov 21;354(6350):245-8
1961251
Science. 1993 Jul 16;261(5119):358-61
8332901
J Biol Chem. 2001 Jul 27;276(30):27806-15
11373296
J Biol Chem. 2001 Jan 5;276(1):729-37
11024037
Genomics. 1998 Mar 1;48(2):163-70
9521869
Hum Mol Genet. 1998 Mar;7(3):325-34
9466987
J Biol Chem. 2002 Dec 6;277(49):47898-906
12324448
J Immunol. 2003 Aug 15;171(4):1901-8
12902492
Mol Cell. 2006 Oct 20;24(2):301-8
17052463
J Immunol. 2006 Jun 15;176(12):7346-53
16751378
J Biol Chem. 2000 Jan 21;275(3):2219-30
10636929
Mol Cell Biol. 2006 Sep;26(18):6832-43
16943425
J Biol Chem. 2002 Jun 21;277(25):22798-805
11934902
J Biol Chem. 2004 Apr 30;279(18):18727-32
14766749
J Biol Chem. 2003 Jan 17;278(3):1841-7
12393887
Nature. 1991 Apr 25;350(6320):706-9
2023632