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Real-time Live Imaging of T-cell Signaling Complex Formation
Published on: June 23, 2013
Structural requirements for beta1 integrin-mediated tyrosine phosphorylation in human T cells
L D Finkelstein1, P J Reynolds, S W Hunt
1Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor 48109, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|April 21, 1998
Summary
The beta1 integrin cytoplasmic domain is essential for tyrosine phosphorylation of HEF1, pp105, and pp115 in T cells. A specific five-amino acid sequence at its C-terminus is critical for this signaling process.
Area of Science:
- Cellular Biology
- Molecular Biology
- Immunology
Background:
- Beta1 integrin receptors initiate signaling pathways triggering tyrosine phosphorylation.
- The beta1 subunit's cytoplasmic domain mediates this phosphorylation but lacks intrinsic kinase activity.
- In H9 T cells, beta1 engagement increases phosphorylation of HEF1, pp105, and pp115, distinct from focal adhesion kinase (FAK).
Purpose of the Study:
- To investigate the role of the beta1 integrin cytoplasmic domain in integrin-mediated tyrosine phosphorylation.
- To identify the specific region within the beta1 cytoplasmic domain responsible for activating phosphorylation of HEF1, pp105, and pp115.
Main Methods:
- Utilized DNA-mediated gene transfer in human T cells.
- Constructed a chimeric receptor combining the beta1 integrin cytoplasmic domain with CD2 antigen extracellular/transmembrane domains.
- Analyzed a series of beta1 cytoplasmic domain truncations.
Main Results:
- The beta1 cytoplasmic domain is both necessary and sufficient for inducing tyrosine phosphorylation of HEF1, pp105, and pp115.
- Truncation of the C-terminal five amino acids of the beta1 cytoplasmic domain abolished phosphorylation signaling.
- The sequence Lys-Tyr-Glu-Gly-Lys (KYEGK) is critical for this phosphorylation cascade.
Conclusions:
- The beta1 integrin cytoplasmic domain plays a crucial role in T cell signaling.
- The C-terminal five amino acids (KYEGK) of the beta1 cytoplasmic domain are essential for coordinating the tyrosine phosphorylation of non-FAK substrates HEF1, pp105, and pp115.
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