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

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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

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Focal Adhesion Kinase 2
Integrin alpha5beta1
Paxillin
Integrins
Natural Killer Cells
Phosphorylation
Protein-Tyrosine Kinases
Tyrosine
Cell Adhesion
Ligation
Fibronectin Receptors
Focal Adhesion Protein-Tyrosine Kinases
Egtazic Acid
Fibronectins

ASJC Scopus subject areas

  • Immunology

Cite this

Proline-Rich Tyrosine Kinase-2 Activation by β1 Integrin Fibronectin Receptor Cross-Linking and Association with Paxillin in Human Natural Killer Cells 1. / Gismondi, Angela; Bisogno, Lorenzo; Mainiero, Fabrizio; Palmieri, Gabriella; Piccoli, Mario; Frati, Luigi; Santoni, Angela.

In: Journal of Immunology, Vol. 159, No. 10, 15.11.1997, p. 4729-4736.

Research output: Contribution to journalArticle

Gismondi, Angela ; Bisogno, Lorenzo ; Mainiero, Fabrizio ; Palmieri, Gabriella ; Piccoli, Mario ; Frati, Luigi ; Santoni, Angela. / Proline-Rich Tyrosine Kinase-2 Activation by β1 Integrin Fibronectin Receptor Cross-Linking and Association with Paxillin in Human Natural Killer Cells 1. In: Journal of Immunology. 1997 ; Vol. 159, No. 10. pp. 4729-4736.
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