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A Novel Interaction between Pyk2 and MAP4K4 Is Integrated with Glioma Cell Migration

Glioma cell migration correlates with Pyk2 activity, but the intrinsic mechanism that regulates the activity of Pyk2 is not fully understood. Previous studies have supported a role for the N-terminal FERM domain in the regulation of Pyk2 activity as mutations in the FERM domain inhibit Pyk2 phosphor...

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Autores principales: Loftus, Joseph C., Yang, Zhongbo, Kloss, Jean, Dhruv, Harshil, Tran, Nhan L., Riggs, Daniel L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791834/
https://www.ncbi.nlm.nih.gov/pubmed/24163766
http://dx.doi.org/10.1155/2013/956580
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author Loftus, Joseph C.
Yang, Zhongbo
Kloss, Jean
Dhruv, Harshil
Tran, Nhan L.
Riggs, Daniel L.
author_facet Loftus, Joseph C.
Yang, Zhongbo
Kloss, Jean
Dhruv, Harshil
Tran, Nhan L.
Riggs, Daniel L.
author_sort Loftus, Joseph C.
collection PubMed
description Glioma cell migration correlates with Pyk2 activity, but the intrinsic mechanism that regulates the activity of Pyk2 is not fully understood. Previous studies have supported a role for the N-terminal FERM domain in the regulation of Pyk2 activity as mutations in the FERM domain inhibit Pyk2 phosphorylation. To search for novel protein-protein interactions mediated by the Pyk2 FERM domain, we utilized a yeast two-hybrid genetic selection to identify the mammalian Ste20 homolog MAP4K4 as a binding partner for the Pyk2 FERM domain. MAP4K4 coimmunoprecipitated with Pyk2 and was a substrate for Pyk2 but did not coimmunoprecipitate with the closely related focal adhesion kinase FAK. Knockdown of MAP4K4 expression inhibited glioma cell migration and effectively blocked Pyk2 stimulation of glioma cell. Increased expression of MAP4K4 stimulated glioma cell migration; however, this stimulation was blocked by knockdown of Pyk2 expression. These data support that the interaction of MAP4K4 and Pyk2 is integrated with glioma cell migration and suggest that inhibition of this interaction may represent a potential therapeutic strategy to limit glioblastoma tumor dispersion.
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spelling pubmed-37918342013-10-27 A Novel Interaction between Pyk2 and MAP4K4 Is Integrated with Glioma Cell Migration Loftus, Joseph C. Yang, Zhongbo Kloss, Jean Dhruv, Harshil Tran, Nhan L. Riggs, Daniel L. J Signal Transduct Research Article Glioma cell migration correlates with Pyk2 activity, but the intrinsic mechanism that regulates the activity of Pyk2 is not fully understood. Previous studies have supported a role for the N-terminal FERM domain in the regulation of Pyk2 activity as mutations in the FERM domain inhibit Pyk2 phosphorylation. To search for novel protein-protein interactions mediated by the Pyk2 FERM domain, we utilized a yeast two-hybrid genetic selection to identify the mammalian Ste20 homolog MAP4K4 as a binding partner for the Pyk2 FERM domain. MAP4K4 coimmunoprecipitated with Pyk2 and was a substrate for Pyk2 but did not coimmunoprecipitate with the closely related focal adhesion kinase FAK. Knockdown of MAP4K4 expression inhibited glioma cell migration and effectively blocked Pyk2 stimulation of glioma cell. Increased expression of MAP4K4 stimulated glioma cell migration; however, this stimulation was blocked by knockdown of Pyk2 expression. These data support that the interaction of MAP4K4 and Pyk2 is integrated with glioma cell migration and suggest that inhibition of this interaction may represent a potential therapeutic strategy to limit glioblastoma tumor dispersion. Hindawi Publishing Corporation 2013 2013-09-15 /pmc/articles/PMC3791834/ /pubmed/24163766 http://dx.doi.org/10.1155/2013/956580 Text en Copyright © 2013 Joseph C. Loftus et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Loftus, Joseph C.
Yang, Zhongbo
Kloss, Jean
Dhruv, Harshil
Tran, Nhan L.
Riggs, Daniel L.
A Novel Interaction between Pyk2 and MAP4K4 Is Integrated with Glioma Cell Migration
title A Novel Interaction between Pyk2 and MAP4K4 Is Integrated with Glioma Cell Migration
title_full A Novel Interaction between Pyk2 and MAP4K4 Is Integrated with Glioma Cell Migration
title_fullStr A Novel Interaction between Pyk2 and MAP4K4 Is Integrated with Glioma Cell Migration
title_full_unstemmed A Novel Interaction between Pyk2 and MAP4K4 Is Integrated with Glioma Cell Migration
title_short A Novel Interaction between Pyk2 and MAP4K4 Is Integrated with Glioma Cell Migration
title_sort novel interaction between pyk2 and map4k4 is integrated with glioma cell migration
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791834/
https://www.ncbi.nlm.nih.gov/pubmed/24163766
http://dx.doi.org/10.1155/2013/956580
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