LYMPHOCYTE ANTIGEN RECEPTOR ACTIVATION OF A FOCAL ADHESION KINASE-RELATED TYROSINE KINASE SUBSTRATE

被引:52
作者
KANNER, SB
ARUFFO, A
CHAN, PY
机构
[1] Bristol-Myers Squibb P., Seattle
[2] Bristol-Myers Squibb, Seattle, WA 98121
关键词
D O I
10.1073/pnas.91.22.10484
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
One of the earliest responses of T and B lymphocytes to stimulation through their antigen receptors is the activation of protein tyrosine kinases and the tyrosine phosphorylation of multiple cellular substrates. Here we describe a tyrosine kinase substrate, fakB, a putative homologue of the focal adhesion kinase ppl25(FAK) Tyrosine phosphorylation of fakB was rapidly augmented in human T and B cells following antigen receptor cross-linking with antibody, while ppl25(FAK) was nonresponsive. Costimulation of the T-cell antigen receptor (TCR/CD3) with either the CD2 or CD4 costimulatory receptors induced synergistic fakB tyrosine phosphorylation in normal human T cells. Engagement of TCR/CD3 induced the stable association of fakB with ZAP-70, the TCR/CD3 xi-chain-associated tyrosine kinase involved in antigen receptor-induced T-cell activation. In addition, preformed complexes of fakB and ZAP-70 were observed in T-cell leukemia lines. Phosphorylation of fakB on serine, threonine, and tyrosine residues was observed both in vivo and in vitro, where a functional increase of in vitro kinase activity was observed following TCR/CD3 stimulation. fakB is thus a focal adhesion kinase-related tyrosine kinase substrate that is differentially regulated from that of pp125(FAK) and likely plays a role in antigen-induced lymphocyte signaling.
引用
收藏
页码:10484 / 10487
页数:4
相关论文
共 25 条