Ephrin kinases and their ephrin ligands transduce repulsion of cells in axon guidance, migration, invasiveness, and tumor growth, exerting a negative signaling on cell proliferation and adhesion. A key role of their kinase activity has been confirmed by mutant kinase inactive receptors that shift the cellular response from repulsion to adhesion. Our present study aimed to investigate the role of low molecular weight protein-tyrosine phosphatase (LMW-PTP) in ephrinA1/EphA2 signaling. LMW-PTP, by means of dephosphorylation of EphA2 kinase, negatively regulates the ephrinA1-mediated repulsive response, cell proliferation, cell adhesion and spreading, and the formation of retraction fibers, thereby confirming the relevance of the net level of tyrosine phosphorylation of Eph receptors. LMW-PTP interferes with ephrin-mediated mitogen-activated protein kinase signaling likely through inhibition of p120RasGAP binding to the activated EphA2 kinase, thereby confirming the key role of mitogen-activated protein kinase inhibition by ephrinA1 repulsive signaling. We conclude that LMW-PTP acts as a terminator of EphA2 signaling causing an efficient negative feedback loop on the biological response mediated by ephrinA1 and pointing on tyrosine phosphorylation as the main event orchestrating the repulsive response.

EphrinA1 repulsive response is regulated by an EphA2 tyrosine phosphatase / M. PARRI; F. BURICCHI; L. TADDEI; E. GIANNONI; G. RAUGEI; G. RAMPONI; P. CHIARUGI. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - STAMPA. - 280(40):(2005), pp. 34008-34018.

EphrinA1 repulsive response is regulated by an EphA2 tyrosine phosphatase

TADDEI, MARIA LETIZIA;GIANNONI, ELISA;RAUGEI, GIOVANNI;RAMPONI, GIAMPIETRO;CHIARUGI, PAOLA
2005

Abstract

Ephrin kinases and their ephrin ligands transduce repulsion of cells in axon guidance, migration, invasiveness, and tumor growth, exerting a negative signaling on cell proliferation and adhesion. A key role of their kinase activity has been confirmed by mutant kinase inactive receptors that shift the cellular response from repulsion to adhesion. Our present study aimed to investigate the role of low molecular weight protein-tyrosine phosphatase (LMW-PTP) in ephrinA1/EphA2 signaling. LMW-PTP, by means of dephosphorylation of EphA2 kinase, negatively regulates the ephrinA1-mediated repulsive response, cell proliferation, cell adhesion and spreading, and the formation of retraction fibers, thereby confirming the relevance of the net level of tyrosine phosphorylation of Eph receptors. LMW-PTP interferes with ephrin-mediated mitogen-activated protein kinase signaling likely through inhibition of p120RasGAP binding to the activated EphA2 kinase, thereby confirming the key role of mitogen-activated protein kinase inhibition by ephrinA1 repulsive signaling. We conclude that LMW-PTP acts as a terminator of EphA2 signaling causing an efficient negative feedback loop on the biological response mediated by ephrinA1 and pointing on tyrosine phosphorylation as the main event orchestrating the repulsive response.
2005
280(40)
34008
34018
M. PARRI; F. BURICCHI; L. TADDEI; E. GIANNONI; G. RAUGEI; G. RAMPONI; P. CHIARUGI
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/252821
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