J Biol Chem. 2003 Sep 19;278(38):36763-76. Epub 2003 Jun 18. Lymphocyte function-associated antigen-1-mediated T cell adhesion is impaired by low molecular weight phosphotyrosine phosphatase-dependent inhibition of FAK activity. Giannoni E, Chiarugi P, Cozzi G, Magnelli L, Taddei ML, Fiaschi T, Buricchi F, Raugei G, Ramponi G. Source Dipartimento di Scienze Biochimiche, Università di Firenze, V.le Morgagni 50, 50134 Firenze, Italy. Abstract Protein tyrosine phosphorylation is one of the earliest signaling events detected in response to lymphocyte function-associated antigen-1 (LFA-1) engagement during lymphocyte adhesion. In particular, the focal adhesion kinase p125FAK, involved in the modulation and rearrangement of the actin cytoskeleton, seems to be a crucial mediator of LFA-1 signaling. Herein, we investigate the role of a FAK tyrosine phosphatase, namely low molecular weight phosphotyrosine phosphatase (LMW-PTP), in the modulation of LFA-1-mediated T cell adhesion. Overexpression of LMW-PTP in Jurkat cells revealed an impairment of LFA-1-dependent cell-cell adhesion upon T cell receptor (TCR) stimulation. Moreover, in these conditions LMW-PTP causes FAK dephosphorylation, thus preventing the activation of FAK downstream pathways. Our results also demonstrated that, upon antigen stimulation, LMW-PTP-dependent FAK inhibition is associated to a strong reduction of LFA-1 and TCR co-clustering toward a single region of T cell surface, thus causing an impairment of receptor activity by preventing changes in their avidity state. Because co-localization of both LFA-1 and TCR is an essential event during encounters of T cells with antigen-presenting cells and immunological synapse (IS) formation, we suggest an intriguing role of LMW-PTP in IS establishment and stabilization through the negative control of FAK activity and, in turn, of cell surface receptor redistribution. PMID: 12815062 [PubMed - indexed for MEDLINE] Free full text

Lymphocyte function-associated antigen-1-mediated T cell adhesion is impaired by low molecular weight phosphotyrosine phosphatase-dependent inhibition of FAK activity / E. GIANNONI; P. CHIARUGI; G. COZZI; L. MAGNELLI; L. TADDEI; T. FIASCHI; F. BURICCHI; G. RAUGEI; G. RAMPONI. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - STAMPA. - 278(38):(2003), pp. 36763-36776. [10.1074/jbc.M302686200]

Lymphocyte function-associated antigen-1-mediated T cell adhesion is impaired by low molecular weight phosphotyrosine phosphatase-dependent inhibition of FAK activity

GIANNONI, ELISA;CHIARUGI, PAOLA;MAGNELLI, LUCIA;TADDEI, MARIA LETIZIA;FIASCHI, TANIA;RAUGEI, GIOVANNI;RAMPONI, GIAMPIETRO
2003

Abstract

J Biol Chem. 2003 Sep 19;278(38):36763-76. Epub 2003 Jun 18. Lymphocyte function-associated antigen-1-mediated T cell adhesion is impaired by low molecular weight phosphotyrosine phosphatase-dependent inhibition of FAK activity. Giannoni E, Chiarugi P, Cozzi G, Magnelli L, Taddei ML, Fiaschi T, Buricchi F, Raugei G, Ramponi G. Source Dipartimento di Scienze Biochimiche, Università di Firenze, V.le Morgagni 50, 50134 Firenze, Italy. Abstract Protein tyrosine phosphorylation is one of the earliest signaling events detected in response to lymphocyte function-associated antigen-1 (LFA-1) engagement during lymphocyte adhesion. In particular, the focal adhesion kinase p125FAK, involved in the modulation and rearrangement of the actin cytoskeleton, seems to be a crucial mediator of LFA-1 signaling. Herein, we investigate the role of a FAK tyrosine phosphatase, namely low molecular weight phosphotyrosine phosphatase (LMW-PTP), in the modulation of LFA-1-mediated T cell adhesion. Overexpression of LMW-PTP in Jurkat cells revealed an impairment of LFA-1-dependent cell-cell adhesion upon T cell receptor (TCR) stimulation. Moreover, in these conditions LMW-PTP causes FAK dephosphorylation, thus preventing the activation of FAK downstream pathways. Our results also demonstrated that, upon antigen stimulation, LMW-PTP-dependent FAK inhibition is associated to a strong reduction of LFA-1 and TCR co-clustering toward a single region of T cell surface, thus causing an impairment of receptor activity by preventing changes in their avidity state. Because co-localization of both LFA-1 and TCR is an essential event during encounters of T cells with antigen-presenting cells and immunological synapse (IS) formation, we suggest an intriguing role of LMW-PTP in IS establishment and stabilization through the negative control of FAK activity and, in turn, of cell surface receptor redistribution. PMID: 12815062 [PubMed - indexed for MEDLINE] Free full text
2003
278(38)
36763
36776
E. GIANNONI; P. CHIARUGI; G. COZZI; L. MAGNELLI; L. TADDEI; T. FIASCHI; F. BURICCHI; G. RAUGEI; G. RAMPONI
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/252834
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