Role of ARHGEF3 as a GEF and mTORC2 Regulator
Guanine nucleotide exchange factors (GEFs) activate GTPases by stimulating the release of guanosine diphosphate to permit the binding of guanosine triphosphate. ARHGEF3 or XPLN (exchange factor found in platelets, leukemic, and neuronal tissues) is a selective guanine nucleotide exchange factor for...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.806258/full |
| _version_ | 1798024663630086144 |
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| author | Sana Abdul Khaliq Sana Abdul Khaliq Zobia Umair Mee-Sup Yoon Mee-Sup Yoon Mee-Sup Yoon |
| author_facet | Sana Abdul Khaliq Sana Abdul Khaliq Zobia Umair Mee-Sup Yoon Mee-Sup Yoon Mee-Sup Yoon |
| author_sort | Sana Abdul Khaliq |
| collection | DOAJ |
| description | Guanine nucleotide exchange factors (GEFs) activate GTPases by stimulating the release of guanosine diphosphate to permit the binding of guanosine triphosphate. ARHGEF3 or XPLN (exchange factor found in platelets, leukemic, and neuronal tissues) is a selective guanine nucleotide exchange factor for Rho GTPases (RhoGEFs) that activates RhoA and RhoB but not RhoC, RhoG, Rac1, or Cdc42. ARHGEF3 contains the diffuse B-cell lymphoma homology and pleckstrin homology domains but lacks similarity with other known functional domains. ARHGEF3 also binds the mammalian target of rapamycin complex 2 (mTORC2) and subsequently inhibits mTORC2 and Akt. In vivo investigation has also indicated the communication between ARHGEF3 and autophagy-related muscle pathologies. Moreover, studies on genetic variation in ARHGEF3 and genome-wide association studies have predicted exciting novel roles of ARHGEF3 in controlling bone mineral density, platelet formation and differentiation, and Hirschsprung disease. In conclusion, we hypothesized that additional biochemical and functional studies are required to elucidate the detailed mechanism of ARHGEF3-related pathologies and therapeutics. |
| first_indexed | 2024-04-11T18:06:18Z |
| format | Article |
| id | doaj.art-5d7de38a235b4b9eae5274d13e828bf3 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-11T18:06:18Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-5d7de38a235b4b9eae5274d13e828bf32022-12-22T04:10:18ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-01-01910.3389/fcell.2021.806258806258Role of ARHGEF3 as a GEF and mTORC2 RegulatorSana Abdul Khaliq0Sana Abdul Khaliq1Zobia Umair2Mee-Sup Yoon3Mee-Sup Yoon4Mee-Sup Yoon5Department of Molecular Medicine, Gachon University College of Medicine, Incheon, South KoreaDepartment of Health Sciences and Technology, GAIHST, Gachon University, Incheon, South KoreaDepartment of Molecular Medicine, Gachon University College of Medicine, Incheon, South KoreaDepartment of Molecular Medicine, Gachon University College of Medicine, Incheon, South KoreaDepartment of Health Sciences and Technology, GAIHST, Gachon University, Incheon, South KoreaLee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, South KoreaGuanine nucleotide exchange factors (GEFs) activate GTPases by stimulating the release of guanosine diphosphate to permit the binding of guanosine triphosphate. ARHGEF3 or XPLN (exchange factor found in platelets, leukemic, and neuronal tissues) is a selective guanine nucleotide exchange factor for Rho GTPases (RhoGEFs) that activates RhoA and RhoB but not RhoC, RhoG, Rac1, or Cdc42. ARHGEF3 contains the diffuse B-cell lymphoma homology and pleckstrin homology domains but lacks similarity with other known functional domains. ARHGEF3 also binds the mammalian target of rapamycin complex 2 (mTORC2) and subsequently inhibits mTORC2 and Akt. In vivo investigation has also indicated the communication between ARHGEF3 and autophagy-related muscle pathologies. Moreover, studies on genetic variation in ARHGEF3 and genome-wide association studies have predicted exciting novel roles of ARHGEF3 in controlling bone mineral density, platelet formation and differentiation, and Hirschsprung disease. In conclusion, we hypothesized that additional biochemical and functional studies are required to elucidate the detailed mechanism of ARHGEF3-related pathologies and therapeutics.https://www.frontiersin.org/articles/10.3389/fcell.2021.806258/fullARHGEF3XPLNrho guanine nucleotide exchange factorsmTORC2Akt |
| spellingShingle | Sana Abdul Khaliq Sana Abdul Khaliq Zobia Umair Mee-Sup Yoon Mee-Sup Yoon Mee-Sup Yoon Role of ARHGEF3 as a GEF and mTORC2 Regulator Frontiers in Cell and Developmental Biology ARHGEF3 XPLN rho guanine nucleotide exchange factors mTORC2 Akt |
| title | Role of ARHGEF3 as a GEF and mTORC2 Regulator |
| title_full | Role of ARHGEF3 as a GEF and mTORC2 Regulator |
| title_fullStr | Role of ARHGEF3 as a GEF and mTORC2 Regulator |
| title_full_unstemmed | Role of ARHGEF3 as a GEF and mTORC2 Regulator |
| title_short | Role of ARHGEF3 as a GEF and mTORC2 Regulator |
| title_sort | role of arhgef3 as a gef and mtorc2 regulator |
| topic | ARHGEF3 XPLN rho guanine nucleotide exchange factors mTORC2 Akt |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.806258/full |
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