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Interaction with the Paxillin LD1 Motif Relieves MEKK2 Auto-inhibition

The cell signaling molecule MEK kinase 2 (MEKK2) is a key upstream regulator of MAPK activity that regulates numerous cellular functions, but the mechanisms that control MEKK2 activity are not well understood. Recently, we reported that MEKK2 both binds and promotes ubiquitylation of the scaffold pr...

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Autores principales: Kahle, Michael P., Cuevas, Bruce D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ubiquity Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831274/
https://www.ncbi.nlm.nih.gov/pubmed/27096002
http://dx.doi.org/10.5334/1750-2187-10-4
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author Kahle, Michael P.
Cuevas, Bruce D.
author_facet Kahle, Michael P.
Cuevas, Bruce D.
author_sort Kahle, Michael P.
collection PubMed
description The cell signaling molecule MEK kinase 2 (MEKK2) is a key upstream regulator of MAPK activity that regulates numerous cellular functions, but the mechanisms that control MEKK2 activity are not well understood. Recently, we reported that MEKK2 both binds and promotes ubiquitylation of the scaffold protein paxillin, and thereby modulates the composition of adhesion complexes. In this study, we have extended our examination of this interaction and report that recombinant paxillin is sufficient to induce MEKK2 auto-phosphorylation. Furthermore, we utilize siRNA-mediated paxillin expression knockdown to reveal that MEKK2 activity is reduced in paxillin-deficient cells. Finally, we show that the paxillin leucine-rich motif 1 (LD1) is sufficient to bind to the MEKK2 amino terminal region and activate MEKK2. Taken together, our results show for the first time that paxillin association promotes MEKK2 activation and reveal the existence of a novel bi-directional regulatory relationship between MEKK2 and paxillin.
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spelling pubmed-48312742016-04-19 Interaction with the Paxillin LD1 Motif Relieves MEKK2 Auto-inhibition Kahle, Michael P. Cuevas, Bruce D. J Mol Signal Research Article The cell signaling molecule MEK kinase 2 (MEKK2) is a key upstream regulator of MAPK activity that regulates numerous cellular functions, but the mechanisms that control MEKK2 activity are not well understood. Recently, we reported that MEKK2 both binds and promotes ubiquitylation of the scaffold protein paxillin, and thereby modulates the composition of adhesion complexes. In this study, we have extended our examination of this interaction and report that recombinant paxillin is sufficient to induce MEKK2 auto-phosphorylation. Furthermore, we utilize siRNA-mediated paxillin expression knockdown to reveal that MEKK2 activity is reduced in paxillin-deficient cells. Finally, we show that the paxillin leucine-rich motif 1 (LD1) is sufficient to bind to the MEKK2 amino terminal region and activate MEKK2. Taken together, our results show for the first time that paxillin association promotes MEKK2 activation and reveal the existence of a novel bi-directional regulatory relationship between MEKK2 and paxillin. Ubiquity Press 2015-10-16 /pmc/articles/PMC4831274/ /pubmed/27096002 http://dx.doi.org/10.5334/1750-2187-10-4 Text en Copyright: © 2015 The Author(s) http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License (CC-BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/3.0/.
spellingShingle Research Article
Kahle, Michael P.
Cuevas, Bruce D.
Interaction with the Paxillin LD1 Motif Relieves MEKK2 Auto-inhibition
title Interaction with the Paxillin LD1 Motif Relieves MEKK2 Auto-inhibition
title_full Interaction with the Paxillin LD1 Motif Relieves MEKK2 Auto-inhibition
title_fullStr Interaction with the Paxillin LD1 Motif Relieves MEKK2 Auto-inhibition
title_full_unstemmed Interaction with the Paxillin LD1 Motif Relieves MEKK2 Auto-inhibition
title_short Interaction with the Paxillin LD1 Motif Relieves MEKK2 Auto-inhibition
title_sort interaction with the paxillin ld1 motif relieves mekk2 auto-inhibition
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831274/
https://www.ncbi.nlm.nih.gov/pubmed/27096002
http://dx.doi.org/10.5334/1750-2187-10-4
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