Proline-Rich Tyrosine Kinase-2 Activation by β1 Integrin Fibronectin Receptor Cross-Linking and Association with Paxillin in Human Natural Killer Cells 1

Angela Gismondi, Lorenzo Bisogno, Fabrizio Mainiero, Gabriella Palmieri, Mario Piccoli, Luigi Frati, Angela Santoni

Research output: Contribution to journalArticle

Abstract

Recent evidence indicates that integrin ligation results in activation of focal adhesion kinase (pp125FAK), the prototype of a new subfamily of nonreceptor protein tyrosine kinase (PTK), including FAKB and the proline-rich tyrosine kinase 2 (PYK-2), also termed cell adhesion kinase-β or related adhesion focal tyrosine kinase. We have previously shown that cross-linking of α4β1 and α5β1 fibronectin receptors on human NK cells stimulates tyrosine phosphorylation of two proteins migrating at 105 and 115 kDa. Here we report that cross-linking of β1 integrins on human NK cells stimulates tyrosine phosphorylation and PTK activity of PYK-2. PYK-2 tyrosine phosphorylation was maximal at 1 min and started to decline 20 min after stimulation. Engagement of α4β1 and α5β1 either with specific mAbs or after cell adhesion to fibronectin or its 120- and 40-kDa fragments also triggered PYK-2 tyrosine phosphorylation. Stimulation of PYK-2 tyrosine phosphorylation was inhibited by the tyrosine kinase inhibitor herbimycin A, but not by EGTA, indicating that PYK-2 tyrosine phosphorylation is PTK, but not calcium, dependent. We also demonstrate that PYK-2 is constitutively associated with paxillin, which undergoes tyrosine phosphorylation with the same kinetics of PYK-2 upon β1 integrin ligation.

Original languageEnglish
Pages (from-to)4729-4736
Number of pages8
JournalJournal of Immunology
Volume159
Issue number10
Publication statusPublished - Nov 15 1997

ASJC Scopus subject areas

  • Immunology

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    Gismondi, A., Bisogno, L., Mainiero, F., Palmieri, G., Piccoli, M., Frati, L., & Santoni, A. (1997). Proline-Rich Tyrosine Kinase-2 Activation by β1 Integrin Fibronectin Receptor Cross-Linking and Association with Paxillin in Human Natural Killer Cells 1. Journal of Immunology, 159(10), 4729-4736.