Proline-rich tyrosine kinase 2 and Rac activation by chemokine and integrin receptors controls NK cell transendothelial migration

Angela Gismondi, Jordan Jacobelli, Raffaele Strippoli, Fabrizio Mainiero, Alessandra Soriani, Loredana Cifaldi, Mario Piccoli, Luigi Frati, Angela Santoni

Research output: Contribution to journalArticle

Abstract

Protein tyrosine kinase activation is an important requisite for leukocyte migration. Herein we demonstrate that NK cell binding to endothelium activates proline-rich tyrosine kinase 2 (Pyk-2) and the small GTP binding protein Rac that are coupled to integrin and chemokine receptors. Chemokine-mediated, but not integrin-mediated, Pyk-2 and Rac activation was sensitive to pretreatment of NK cells with pertussis toxin, a pharmacological inhibitor of G i protein-coupled receptors. Both Pyk-2 and Rac are functionally involved in chemokine-induced NK cell migration through endothelium or ICAM-1 or VCAM-1 adhesive proteins, as shown by the use of recombinant vaccinia viruses encoding dominant negative mutants of Pyk-2 and Rac. Moreover, we found that Pyk-2 is associated with the Rac guanine nucleotide exchange factor Vav, which undergoes tyrosine phosphorylation upon integrin triggering. Finally, we provide direct evidence for the involvement of Pyk-2 in the control of both chemokine- and integrin-mediated Rac activation. Collectively, our results indicate that Pyk-2 acts as a receptor-proximal link between integrin and chemokine receptor signaling, and the Pyk-2/Rac pathway plays a pivotal role in the control of NK cell transendothelial migration.

Original languageEnglish
Pages (from-to)3065-3073
Number of pages9
JournalJournal of Immunology
Volume170
Issue number6
Publication statusPublished - Mar 15 2003

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Proline-rich tyrosine kinase 2 and Rac activation by chemokine and integrin receptors controls NK cell transendothelial migration'. Together they form a unique fingerprint.

  • Cite this

    Gismondi, A., Jacobelli, J., Strippoli, R., Mainiero, F., Soriani, A., Cifaldi, L., Piccoli, M., Frati, L., & Santoni, A. (2003). Proline-rich tyrosine kinase 2 and Rac activation by chemokine and integrin receptors controls NK cell transendothelial migration. Journal of Immunology, 170(6), 3065-3073.