Sprouty4 is an endogenous negative modulator of TrkA signaling and neuronal differentiation induced by NGF.

The Sprouty (Spry) family of proteins represents endogenous regulators of downstream signaling pathways induced by receptor tyrosine kinases (RTKs). Using real time PCR, we detect a significant increase in the expression of Spry4 mRNA in response to NGF, indicating that Spry4 could modulate intracel...

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Autores principales:	Fernando C Alsina, Dolores Irala, Paula A Fontanet, Francisco J Hita, Fernanda Ledda, Gustavo Paratcha
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/26f08dc99e1e46218f686c5a1c274ebe
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spelling	oai:doaj.org-article:26f08dc99e1e46218f686c5a1c274ebe2021-11-18T07:26:54ZSprouty4 is an endogenous negative modulator of TrkA signaling and neuronal differentiation induced by NGF.1932-620310.1371/journal.pone.0032087https://doaj.org/article/26f08dc99e1e46218f686c5a1c274ebe2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22384148/?tool=EBIhttps://doaj.org/toc/1932-6203The Sprouty (Spry) family of proteins represents endogenous regulators of downstream signaling pathways induced by receptor tyrosine kinases (RTKs). Using real time PCR, we detect a significant increase in the expression of Spry4 mRNA in response to NGF, indicating that Spry4 could modulate intracellular signaling pathways and biological processes induced by NGF and its receptor TrkA. In this work, we demonstrate that overexpression of wild-type Spry4 causes a significant reduction in MAPK and Rac1 activation and neurite outgrowth induced by NGF. At molecular level, our findings indicate that ectopic expression of a mutated form of Spry4 (Y53A), in which a conserved tyrosine residue was replaced, fail to block both TrkA-mediated Erk/MAPK activation and neurite outgrowth induced by NGF, suggesting that an intact tyrosine 53 site is required for the inhibitory effect of Spry4 on NGF signaling. Downregulation of Spry4 using small interference RNA knockdown experiments potentiates PC12 cell differentiation and MAPK activation in response to NGF. Together, these findings establish a new physiological mechanism through which Spry4 regulates neurite outgrowth reducing not only the MAPK pathway but also restricting Rac1 activation in response to NGF.Fernando C AlsinaDolores IralaPaula A FontanetFrancisco J HitaFernanda LeddaGustavo ParatchaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e32087 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fernando C Alsina Dolores Irala Paula A Fontanet Francisco J Hita Fernanda Ledda Gustavo Paratcha Sprouty4 is an endogenous negative modulator of TrkA signaling and neuronal differentiation induced by NGF.
description	The Sprouty (Spry) family of proteins represents endogenous regulators of downstream signaling pathways induced by receptor tyrosine kinases (RTKs). Using real time PCR, we detect a significant increase in the expression of Spry4 mRNA in response to NGF, indicating that Spry4 could modulate intracellular signaling pathways and biological processes induced by NGF and its receptor TrkA. In this work, we demonstrate that overexpression of wild-type Spry4 causes a significant reduction in MAPK and Rac1 activation and neurite outgrowth induced by NGF. At molecular level, our findings indicate that ectopic expression of a mutated form of Spry4 (Y53A), in which a conserved tyrosine residue was replaced, fail to block both TrkA-mediated Erk/MAPK activation and neurite outgrowth induced by NGF, suggesting that an intact tyrosine 53 site is required for the inhibitory effect of Spry4 on NGF signaling. Downregulation of Spry4 using small interference RNA knockdown experiments potentiates PC12 cell differentiation and MAPK activation in response to NGF. Together, these findings establish a new physiological mechanism through which Spry4 regulates neurite outgrowth reducing not only the MAPK pathway but also restricting Rac1 activation in response to NGF.
format	article
author	Fernando C Alsina Dolores Irala Paula A Fontanet Francisco J Hita Fernanda Ledda Gustavo Paratcha
author_facet	Fernando C Alsina Dolores Irala Paula A Fontanet Francisco J Hita Fernanda Ledda Gustavo Paratcha
author_sort	Fernando C Alsina
title	Sprouty4 is an endogenous negative modulator of TrkA signaling and neuronal differentiation induced by NGF.
title_short	Sprouty4 is an endogenous negative modulator of TrkA signaling and neuronal differentiation induced by NGF.
title_full	Sprouty4 is an endogenous negative modulator of TrkA signaling and neuronal differentiation induced by NGF.
title_fullStr	Sprouty4 is an endogenous negative modulator of TrkA signaling and neuronal differentiation induced by NGF.
title_full_unstemmed	Sprouty4 is an endogenous negative modulator of TrkA signaling and neuronal differentiation induced by NGF.
title_sort	sprouty4 is an endogenous negative modulator of trka signaling and neuronal differentiation induced by ngf.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/26f08dc99e1e46218f686c5a1c274ebe
work_keys_str_mv	AT fernandocalsina sprouty4isanendogenousnegativemodulatoroftrkasignalingandneuronaldifferentiationinducedbyngf AT doloresirala sprouty4isanendogenousnegativemodulatoroftrkasignalingandneuronaldifferentiationinducedbyngf AT paulaafontanet sprouty4isanendogenousnegativemodulatoroftrkasignalingandneuronaldifferentiationinducedbyngf AT franciscojhita sprouty4isanendogenousnegativemodulatoroftrkasignalingandneuronaldifferentiationinducedbyngf AT fernandaledda sprouty4isanendogenousnegativemodulatoroftrkasignalingandneuronaldifferentiationinducedbyngf AT gustavoparatcha sprouty4isanendogenousnegativemodulatoroftrkasignalingandneuronaldifferentiationinducedbyngf
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Sprouty4 is an endogenous negative modulator of TrkA signaling and neuronal differentiation induced by NGF.

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