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Pyk2 Controls Integrin-Dependent CTL Migration through Regulation of De-Adhesion
Samuel M S Cheung1, Hanne L Ostergaard2
1Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.
Journal of Immunology (Baltimore, Md. : 1950)
|July 27, 2016
Summary
Protein tyrosine kinase 2 (Pyk2) regulates T cell migration by controlling detachment from ICAM-1. Inhibiting Pyk2 impairs CTL mobility, causing defects in detachment at the trailing edge.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Protein tyrosine kinase 2 (Pyk2) plays a role in T cell adhesion to ICAM-1.
- The precise mechanism of Pyk2's regulation of T cell adhesion and migration is not fully understood.
Purpose of the Study:
- To investigate the mechanism by which Pyk2 regulates T cell adhesion and migration on ICAM-1.
- To determine the role of Pyk2 in the dynamic processes of T cell movement.
Main Methods:
- Disruption of Pyk2 function using pharmacological inhibition, siRNA knockdown, and dominant-negative expression.
- Live-cell imaging to observe T cell adhesion and migration dynamics on ICAM-1.
- Analysis of Pyk2 tyrosine phosphorylation localization in migrating T cells.
Main Results:
- Pyk2 is not essential for initial T cell adhesion but delays it, with disruption leading to abnormally strong adhesion.
- Impaired Pyk2 function severely compromises T cell random mobility on ICAM-1.
- Live-cell imaging revealed defects in trailing edge detachment from ICAM-1 upon Pyk2 inhibition.
- Spatially regulated Pyk2 tyrosine phosphorylation (Y579/Y580 at leading edge, Y881 at trailing edge) was observed.
- Inhibition of Pyk2 resulted in multiple LFA-1-rich tails, indicating a defect in LFA-1 release.
Conclusions:
- Pyk2 is crucial for regulating T cell detachment at the trailing edge during migration on ICAM-1.
- This regulation of detachment by Pyk2 is essential for efficient T cell migration and chemotaxis.
- Pyk2's role in detachment may explain its importance in T cell migratory responses.
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