RAPID T-CELL RECEPTOR-MEDIATED TYROSINE PHOSPHORYLATION OF P120, AN FYN/LCK SRC HOMOLOGY-3 DOMAIN-BINDING PROTEIN

被引:84
作者
REEDQUIST, KA
FUKAZAWA, T
DRUKER, B
PANCHAMOORTHY, G
SHOELSON, SE
BAND, H
机构
[1] HARVARD UNIV, BRIGHAM & WOMENS HOSP,SCH MED, DEPT RHEUMATOL & IMMUNOL,LYMPHOCYTE BIOL SECT, BOSTON, MA 02115 USA
[2] HARVARD UNIV, BRIGHAM & WOMENS HOSP,SCH MED,JOSLIN DIABET CTR, DEPT MED,DIV RES, BOSTON, MA 02115 USA
[3] OREGON HLTH SCI UNIV, DIV HEMATOL & MED ONCOL, PORTLAND, OR 97201 USA
关键词
T-CELL ACTIVATION; SIGNAL TRANSDUCTION; PROTEIN-TYROSINE KINASE; SRC-FAMILY KINASES;
D O I
10.1073/pnas.91.10.4135
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Tyrosine phosphorylation of cellular proteins is the earliest identifiable event following T-cell antigen receptor (TCR) stimulation and is essential for activating downstream signaling machinery. Two Src-family protein-tyrosine kinases, the TCR-associated p59(fyn) (Fyn) and the CD4/8-associated p56(lck) (Lck), have emerged as the likely mediators of early tyrosine phosphorylation in T cells. Here, we show direct binding of a 120-kDa TCR-induced phosphotyrosyl polypeptide, p120, to glutathione S-transferase fusion proteins of the Src homology 3 (SH3) domains of Fyn, Lck, and p60(Src) (Src) but not other proteins. While binding of p120 to Fyn SH2 domain was phosphotyrosine-dependent as expected, its binding to the SH3 domain was independent of tyrosine phosphorylation, as shown by lack of competition with a phosphotyrosyl competitor peptide. In contrast, an SH3-specific proline-rich peptide completely abolished p120 binding to SH3. p120 was tyrosine-phosphorylated within 10 sec following stimulation of Jurkat cells with anti-CD3 monoclonal antibody, with maximal phosphorylation at 30 sec. Importantly, p120 was found associated with Fyn and Lck proteins in unstimulated Jurkat cells and served as an in vitro substrate for these kinases. These results provide evidence for a role of the SH3 domains of Fyn and Lck in the recruitment of early tyrosine-phosphorylation substrates to the TCR-associated tyrosine kinases.
引用
收藏
页码:4135 / 4139
页数:5
相关论文
共 36 条
[1]   DEFECTIVE T-CELL RECEPTOR SIGNALING IN MICE LACKING THE THYMIC ISOFORM OF P59(FYN) [J].
APPLEBY, MW ;
GROSS, JA ;
COOKE, MP ;
LEVIN, SD ;
QIAN, X ;
PERLMUTTER, RM .
CELL, 1992, 70 (05) :751-763
[2]   STRUCTURAL REQUIREMENTS FOR ENHANCEMENT OF T-CELL RESPONSIVENESS BY THE LYMPHOCYTE-SPECIFIC TYROSINE PROTEIN-KINASE P56LCK [J].
CARON, L ;
ABRAHAM, N ;
PAWSON, T ;
VEILLETTE, A .
MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (06) :2720-2729
[3]  
CARPENTER CL, 1993, J BIOL CHEM, V268, P9478
[4]   ZAP-70 - A 70 KD PROTEIN-TYROSINE KINASE THAT ASSOCIATES WITH THE TCR ZETA-CHAIN [J].
CHAN, AC ;
IWASHIMA, M ;
TURCK, CW ;
WEISS, A .
CELL, 1992, 71 (04) :649-662
[5]   IDENTIFICATION OF A PROTEIN THAT BINDS TO THE SH3 REGION OF ABI AND IS SIMILAR TO BCR AND GAP-RHO [J].
CICCHETTI, P ;
MAYER, BJ ;
THIEL, G ;
BALTIMORE, D .
SCIENCE, 1992, 257 (5071) :803-806
[6]   REGULATION OF T-CELL RECEPTOR SIGNALING BY A SRC FAMILY PROTEIN-TYROSINE KINASE (P59FYN) [J].
COOKE, MP ;
ABRAHAM, KM ;
FORBUSH, KA ;
PERLMUTTER, RM .
CELL, 1991, 65 (02) :281-291
[7]   THE WHEN AND HOW OF SRC REGULATION [J].
COOPER, JA ;
HOWELL, B .
CELL, 1993, 73 (06) :1051-1054
[8]   T-CELL RECEPTOR-ZETA CD3-P59(FYN(T))-ASSOCIATED P120/130 BINDS TO THE SH2 DOMAIN OF P59(FYN(T)) [J].
DASILVA, AJ ;
JANSSEN, O ;
RUDD, CE .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (06) :2107-2113
[9]   DIFFERENTIAL REGULATION OF T-CELL ANTIGEN RESPONSIVENESS BY ISOFORMS OF THE SRC-RELATED TYROSINE PROTEIN-KINASE P59FYN [J].
DAVIDSON, D ;
CHOW, LML ;
FOURNEL, M ;
VEILLETTE, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 175 (06) :1483-1492
[10]   INHIBITION OF SH2 DOMAIN PHOSPHOPROTEIN ASSOCIATION BY A NONHYDROLYZABLE PHOSPHONOPEPTIDE [J].
DOMCHEK, SM ;
AUGER, KR ;
CHATTERJEE, S ;
BURKE, TR ;
SHOELSON, SE .
BIOCHEMISTRY, 1992, 31 (41) :9865-9870