Phosphorylation of CrkL S114 induced by common gamma chain cytokines and T-cell receptor signal transduction

Abstract T-cell activation and cellular expansion by common gamma chain cytokines such as Interleukin-2 is necessary for adaptive immunity. However, when unregulated these same pathways promote pathologies ranging from autoimmune disorders to cancer. While the functional role of Interleukin-2 and do...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Armando Estrada, Alejandro C. Rodriguez, Georgialina Rodriguez, Alice H. Grant, Yoshira M. Ayala-Marin, Amy J. Arrieta, Robert A. Kirken
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9512cc6ef415433aa641845f6ef594ca
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9512cc6ef415433aa641845f6ef594ca
record_format	dspace
spelling	oai:doaj.org-article:9512cc6ef415433aa641845f6ef594ca2021-12-02T16:46:35ZPhosphorylation of CrkL S114 induced by common gamma chain cytokines and T-cell receptor signal transduction10.1038/s41598-021-96428-y2045-2322https://doaj.org/article/9512cc6ef415433aa641845f6ef594ca2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96428-yhttps://doaj.org/toc/2045-2322Abstract T-cell activation and cellular expansion by common gamma chain cytokines such as Interleukin-2 is necessary for adaptive immunity. However, when unregulated these same pathways promote pathologies ranging from autoimmune disorders to cancer. While the functional role of Interleukin-2 and downstream effector molecules is relatively clear, the repertoire of phosphoregulatory proteins downstream of this pathway is incomplete. To identify phosphoproteins downstream of common gamma chain receptor, YT cells were radiolabeled with [32P]-orthophosphate and stimulated with Interleukin-2. Subsequently, tyrosine phosphorylated proteins were immunopurified and subjected to tandem mass spectrometry—leading to the identification of CrkL. Phosphoamino acid analysis revealed concurrent serine phosphorylation of CrkL and was later identified as S114 by mass spectrometry analysis. S114 was inducible through stimulation with Interleukin-2 or T-cell receptor stimulation. Polyclonal antibodies were generated against CrkL phospho-S114, and used to show its inducibility by multiple stimuli. These findings confirm CrkL as an Interleukin-2 responsive protein that becomes phosphorylated at S114 by a kinase/s downstream of PI3K and MEK/ERK signaling.Armando EstradaAlejandro C. RodriguezGeorgialina RodriguezAlice H. GrantYoshira M. Ayala-MarinAmy J. ArrietaRobert A. KirkenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Armando Estrada Alejandro C. Rodriguez Georgialina Rodriguez Alice H. Grant Yoshira M. Ayala-Marin Amy J. Arrieta Robert A. Kirken Phosphorylation of CrkL S114 induced by common gamma chain cytokines and T-cell receptor signal transduction
description	Abstract T-cell activation and cellular expansion by common gamma chain cytokines such as Interleukin-2 is necessary for adaptive immunity. However, when unregulated these same pathways promote pathologies ranging from autoimmune disorders to cancer. While the functional role of Interleukin-2 and downstream effector molecules is relatively clear, the repertoire of phosphoregulatory proteins downstream of this pathway is incomplete. To identify phosphoproteins downstream of common gamma chain receptor, YT cells were radiolabeled with [32P]-orthophosphate and stimulated with Interleukin-2. Subsequently, tyrosine phosphorylated proteins were immunopurified and subjected to tandem mass spectrometry—leading to the identification of CrkL. Phosphoamino acid analysis revealed concurrent serine phosphorylation of CrkL and was later identified as S114 by mass spectrometry analysis. S114 was inducible through stimulation with Interleukin-2 or T-cell receptor stimulation. Polyclonal antibodies were generated against CrkL phospho-S114, and used to show its inducibility by multiple stimuli. These findings confirm CrkL as an Interleukin-2 responsive protein that becomes phosphorylated at S114 by a kinase/s downstream of PI3K and MEK/ERK signaling.
format	article
author	Armando Estrada Alejandro C. Rodriguez Georgialina Rodriguez Alice H. Grant Yoshira M. Ayala-Marin Amy J. Arrieta Robert A. Kirken
author_facet	Armando Estrada Alejandro C. Rodriguez Georgialina Rodriguez Alice H. Grant Yoshira M. Ayala-Marin Amy J. Arrieta Robert A. Kirken
author_sort	Armando Estrada
title	Phosphorylation of CrkL S114 induced by common gamma chain cytokines and T-cell receptor signal transduction
title_short	Phosphorylation of CrkL S114 induced by common gamma chain cytokines and T-cell receptor signal transduction
title_full	Phosphorylation of CrkL S114 induced by common gamma chain cytokines and T-cell receptor signal transduction
title_fullStr	Phosphorylation of CrkL S114 induced by common gamma chain cytokines and T-cell receptor signal transduction
title_full_unstemmed	Phosphorylation of CrkL S114 induced by common gamma chain cytokines and T-cell receptor signal transduction
title_sort	phosphorylation of crkl s114 induced by common gamma chain cytokines and t-cell receptor signal transduction
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9512cc6ef415433aa641845f6ef594ca
work_keys_str_mv	AT armandoestrada phosphorylationofcrkls114inducedbycommongammachaincytokinesandtcellreceptorsignaltransduction AT alejandrocrodriguez phosphorylationofcrkls114inducedbycommongammachaincytokinesandtcellreceptorsignaltransduction AT georgialinarodriguez phosphorylationofcrkls114inducedbycommongammachaincytokinesandtcellreceptorsignaltransduction AT alicehgrant phosphorylationofcrkls114inducedbycommongammachaincytokinesandtcellreceptorsignaltransduction AT yoshiramayalamarin phosphorylationofcrkls114inducedbycommongammachaincytokinesandtcellreceptorsignaltransduction AT amyjarrieta phosphorylationofcrkls114inducedbycommongammachaincytokinesandtcellreceptorsignaltransduction AT robertakirken phosphorylationofcrkls114inducedbycommongammachaincytokinesandtcellreceptorsignaltransduction
_version_	1718383410232164352

Phosphorylation of CrkL S114 induced by common gamma chain cytokines and T-cell receptor signal transduction

Ejemplares similares