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Structure analysis between the SWAP-70 RHO-GEF and the newly described PLD2-GEF

Small GTPases like Rac2 are crucial regulators of many cell functions central to life itself. Our laboratory has recently found that phospholipase D2 (PLD2) can act as a guanine nucleotide exchange factor (GEF) for Rac2. PLD2 has a Pleckstrin Homology (PH) domain but does not bear a Dbl homology (DH...

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Autor principal: Gomez-Cambronero, Julian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Landes Bioscience 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520882/
https://www.ncbi.nlm.nih.gov/pubmed/22858691
http://dx.doi.org/10.4161/sgtp.20887
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author Gomez-Cambronero, Julian
author_facet Gomez-Cambronero, Julian
author_sort Gomez-Cambronero, Julian
collection PubMed
description Small GTPases like Rac2 are crucial regulators of many cell functions central to life itself. Our laboratory has recently found that phospholipase D2 (PLD2) can act as a guanine nucleotide exchange factor (GEF) for Rac2. PLD2 has a Pleckstrin Homology (PH) domain but does not bear a Dbl homology (DH) or DOCK homology region (DHR) domain. It has, however, a Phox (PX) domain upstream of its PH domain. To better understand the novel finding of PLD2 as an enhancer of GDP/GTP exchange, we modeled the N-terminal portion of PLD2 (as the crystal structure of this protein has not as of yet been resolved), and studied the correlation with two known GEFs, SWAP-70 and the Leukemic Associated RhoGEF (LARG). Structural similarities between PLD2’s PH and SWAP-70s or LARG’s PH domain are very extensive, while similarities between PLD2’s PX and SWAP-70s or LARG’s DH domains are less evident. This indicates that PLD functions as a GEF utilizing its PH domain and part of its PX domain and possibly other regions. All this makes PLD unique, and an entirely new class of GEF. By bearing two enzymatic activities (break down of PC and GDP/GTP exchange), it is realistic to assume that PLD is an important signaling node for several intracellular pathways. Future experiments will ascertain how the newly described PLD2’s GEF is regulated in the context of cell activation.
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spelling pubmed-35208822012-12-17 Structure analysis between the SWAP-70 RHO-GEF and the newly described PLD2-GEF Gomez-Cambronero, Julian Small GTPases Letter to the Editor Small GTPases like Rac2 are crucial regulators of many cell functions central to life itself. Our laboratory has recently found that phospholipase D2 (PLD2) can act as a guanine nucleotide exchange factor (GEF) for Rac2. PLD2 has a Pleckstrin Homology (PH) domain but does not bear a Dbl homology (DH) or DOCK homology region (DHR) domain. It has, however, a Phox (PX) domain upstream of its PH domain. To better understand the novel finding of PLD2 as an enhancer of GDP/GTP exchange, we modeled the N-terminal portion of PLD2 (as the crystal structure of this protein has not as of yet been resolved), and studied the correlation with two known GEFs, SWAP-70 and the Leukemic Associated RhoGEF (LARG). Structural similarities between PLD2’s PH and SWAP-70s or LARG’s PH domain are very extensive, while similarities between PLD2’s PX and SWAP-70s or LARG’s DH domains are less evident. This indicates that PLD functions as a GEF utilizing its PH domain and part of its PX domain and possibly other regions. All this makes PLD unique, and an entirely new class of GEF. By bearing two enzymatic activities (break down of PC and GDP/GTP exchange), it is realistic to assume that PLD is an important signaling node for several intracellular pathways. Future experiments will ascertain how the newly described PLD2’s GEF is regulated in the context of cell activation. Landes Bioscience 2012-10-01 /pmc/articles/PMC3520882/ /pubmed/22858691 http://dx.doi.org/10.4161/sgtp.20887 Text en Copyright © 2012 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Letter to the Editor
Gomez-Cambronero, Julian
Structure analysis between the SWAP-70 RHO-GEF and the newly described PLD2-GEF
title Structure analysis between the SWAP-70 RHO-GEF and the newly described PLD2-GEF
title_full Structure analysis between the SWAP-70 RHO-GEF and the newly described PLD2-GEF
title_fullStr Structure analysis between the SWAP-70 RHO-GEF and the newly described PLD2-GEF
title_full_unstemmed Structure analysis between the SWAP-70 RHO-GEF and the newly described PLD2-GEF
title_short Structure analysis between the SWAP-70 RHO-GEF and the newly described PLD2-GEF
title_sort structure analysis between the swap-70 rho-gef and the newly described pld2-gef
topic Letter to the Editor
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520882/
https://www.ncbi.nlm.nih.gov/pubmed/22858691
http://dx.doi.org/10.4161/sgtp.20887
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