Lymphocyte antigen receptor activation of a focal adhesion kinase-related tyrosine kinase substrate

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Updated: Oct 24, 2026

Real-time Live Imaging of T-cell Signaling Complex Formation
10:31

Real-time Live Imaging of T-cell Signaling Complex Formation

Published on: June 23, 2013

S B Kanner1, A Aruffo, P Y Chan

  • 1Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.

Proceedings of the National Academy of Sciences of the United States of America
|October 25, 1994
PubMed

Insights

Researchers identified fakB, a novel tyrosine kinase substrate, crucial for lymphocyte signaling. FakB phosphorylation increases upon antigen receptor stimulation, unlike pp125FAK, suggesting a key role in T and B cell activation.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Lymphocyte activation via antigen receptors involves protein tyrosine kinase signaling.
  • Multiple cellular substrates undergo tyrosine phosphorylation upon T and B cell stimulation.

Purpose of the Study:

  • To identify and characterize novel tyrosine kinase substrates involved in lymphocyte activation.
  • To investigate the role of fakB, a homologue of focal adhesion kinase pp125FAK, in T and B cell signaling.

Main Methods:

  • Utilized human T and B cells, antigen receptor cross-linking with antibodies.
  • Employed costimulation with T-cell receptor (TCR/CD3) and CD2 or CD4 receptors.
  • Analyzed protein tyrosine phosphorylation, complex formation with ZAP-70, and in vitro kinase activity.

Main Results:

  • Tyrosine phosphorylation of fakB was rapidly augmented in T and B cells after antigen receptor stimulation, while pp125FAK remained unresponsive.
  • Costimulation of TCR/CD3 with CD2 or CD4 synergistically enhanced fakB tyrosine phosphorylation in T cells.
  • fakB formed stable complexes with ZAP-70, a key tyrosine kinase in T-cell activation, and showed increased in vitro kinase activity post-TCR/CD3 stimulation.

Conclusions:

  • fakB is a focal adhesion kinase-related tyrosine kinase substrate differentially regulated compared to pp125FAK.
  • fakB likely plays a significant role in antigen-induced lymphocyte signaling pathways.

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