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Jian-kang Zhu - One of the best experts on this subject based on the ideXlab platform.
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the plasma membrane polyamine transporter put3 is regulated by the na h antiporter SOS1 and protein kinase sos2
New Phytologist, 2020Co-Authors: Jian-kang Zhu, Haoxi Chai, Jianfei Guo, Yingli Zhong, Chuan-chih Hsu, Changsong Zou, Pengcheng Wang, Huazhong ShiAbstract:In Arabidopsis, the plasma membrane transporter PUT3 is important to maintain the cellular homeostasis of polyamines and plays a role in stabilizing mRNAs of some heat-inducible genes. The plasma membrane Na+ /H+ transporter SOS1 and the protein kinase SOS2 are two salt-tolerance determinants crucial for maintaining intracellular Na+ and K+ homeostasis. Here, we report that PUT3 genetically and physically interacts with SOS1 and SOS2, and these interactions modulate PUT3 transport activity. Overexpression of PUT3 (PUT3OE) results in hypersensitivity of the transgenic plants to polyamine and paraquat. The hypersensitivity of PUT3OE is inhibited by the SOS1 and sos2 mutations, which indicates that SOS1 and SOS2 are required for PUT3 transport activity. A protein interaction assay revealed that PUT3 physically interacts with SOS1 and SOS2 in yeast and plant cells. SOS2 phosphorylates PUT3 both in vitro and in vivo. SOS1 and SOS2 synergistically activate the polyamine transport activity of PUT3, and PUT3 also modulates SOS1 activity by activating SOS2 in yeast cells. Overall, our findings suggest that both plasma-membrane proteins PUT3 and SOS1 could form a complex with the protein kinase SOS2 in response to stress conditions and modulate the transport activity of each other through protein interactions and phosphorylation.
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The plasma-membrane polyamine transporter PUT3 is regulated by the Na+ /H+ antiporter SOS1 and protein kinase SOS2.
The New phytologist, 2020Co-Authors: Haoxi Chai, Jian-kang Zhu, Jianfei Guo, Yingli Zhong, Chuan-chih Hsu, Changsong Zou, Pengcheng Wang, Huazhong ShiAbstract:In Arabidopsis, the plasma membrane transporter PUT3 is important to maintain the cellular homeostasis of polyamines and plays a role in stabilizing mRNAs of some heat-inducible genes. The plasma membrane Na+ /H+ transporter SOS1 and the protein kinase SOS2 are two salt-tolerance determinants crucial for maintaining intracellular Na+ and K+ homeostasis. Here, we report that PUT3 genetically and physically interacts with SOS1 and SOS2, and these interactions modulate PUT3 transport activity. Overexpression of PUT3 (PUT3OE) results in hypersensitivity of the transgenic plants to polyamine and paraquat. The hypersensitivity of PUT3OE is inhibited by the SOS1 and sos2 mutations, which indicates that SOS1 and SOS2 are required for PUT3 transport activity. A protein interaction assay revealed that PUT3 physically interacts with SOS1 and SOS2 in yeast and plant cells. SOS2 phosphorylates PUT3 both in vitro and in vivo. SOS1 and SOS2 synergistically activate the polyamine transport activity of PUT3, and PUT3 also modulates SOS1 activity by activating SOS2 in yeast cells. Overall, our findings suggest that both plasma-membrane proteins PUT3 and SOS1 could form a complex with the protein kinase SOS2 in response to stress conditions and modulate the transport activity of each other through protein interactions and phosphorylation.
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activation of the plasma membrane na h antiporter salt overly sensitive 1 SOS1 by phosphorylation of an auto inhibitory c terminal domain
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Francisco J. Quintero, Jian-kang Zhu, Juliana Martinezatienza, Irene Villalta, Xingyu Jiang, Woeyeo Kim, Zhai Ali, Hiroaki Fujii, Imelda Mendoza, José M. PardoAbstract:The plasma membrane sodium/proton exchanger Salt-Overly-Sensitive 1 (SOS1) is a critical salt tolerance determinant in plants. The SOS2–SOS3 calcium-dependent protein kinase complex up-regulates SOS1 activity, but the mechanistic details of this crucial event remain unresolved. Here we show that SOS1 is maintained in a resting state by a C-terminal auto-inhibitory domain that is the target of SOS2–SOS3. The auto-inhibitory domain interacts intramolecularly with an adjacent domain of SOS1 that is essential for activity. SOS1 is relieved from auto-inhibition upon phosphorylation of the auto-inhibitory domain by SOS2–SOS3. Mutation of the SOS2 phosphorylation and recognition site impeded the activation of SOS1 in vivo and in vitro. Additional amino acid residues critically important for SOS1 activity and regulation were identified in a genetic screen for hypermorphic alleles.
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reactive oxygen species mediate na induced SOS1 mrna stability in arabidopsis
Plant Journal, 2007Co-Authors: Jung-sung Chung, Jian-kang Zhu, Ray A. Bressan, Paul M. Hasegawa, Huazhong ShiAbstract:*Summary Salt Overly Sensitive 1 (SOS1), a plasma membrane Na+ /H + antiporter in Arabidopsis, is a salt tolerance determinant crucial for the maintenance of ion homeostasis in saline stress conditions. SOS1 mRNA is unstable at normal growth conditions, but its stability is substantially increased under salt stress and other ionic and dehydration stresses. In addition, H 2O2 treatment increases the stability of SOS1 mRNA. SOS1 mRNA is inherently unstable and rapidly degraded with a half-life of approximately 10 min. Rapid decay of SOS1 mRNA requires new protein synthesis. Stress-induced SOS1 mRNA stability is mediated by reactive oxygen species (ROS). NADPH oxidase is also involved in the upregulation of SOS1 mRNA stability, presumably through the control of extracellular ROS production. The cis-element required for SOS1 mRNA instability resides in the 500-bp region within the 2.2 kb at the 3¢ end of the SOS1 mRNA. Furthermore, mutations in the SOS1 gene render SOS1 mutants more tolerant to paraquat, a non-selective herbicide causing oxidative stress, indicating that SOS1 plays negative roles in tolerance of oxidative stress. A hypothetical model for the signaling pathway involving SOS1-mediated pH changes, NADPH oxidase activation, apoplastic ROS production and downstream signaling transduction is proposed, and the biological significance of ROS-mediated induction of SOS1 mRNA stability is discussed.
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Reactive oxygen species mediate Na+-induced SOS1 mRNA stability in Arabidopsis
The Plant journal : for cell and molecular biology, 2007Co-Authors: Jung-sung Chung, Jian-kang Zhu, Ray A. Bressan, Paul M. Hasegawa, Huazhong ShiAbstract:*Summary Salt Overly Sensitive 1 (SOS1), a plasma membrane Na+ /H + antiporter in Arabidopsis, is a salt tolerance determinant crucial for the maintenance of ion homeostasis in saline stress conditions. SOS1 mRNA is unstable at normal growth conditions, but its stability is substantially increased under salt stress and other ionic and dehydration stresses. In addition, H 2O2 treatment increases the stability of SOS1 mRNA. SOS1 mRNA is inherently unstable and rapidly degraded with a half-life of approximately 10 min. Rapid decay of SOS1 mRNA requires new protein synthesis. Stress-induced SOS1 mRNA stability is mediated by reactive oxygen species (ROS). NADPH oxidase is also involved in the upregulation of SOS1 mRNA stability, presumably through the control of extracellular ROS production. The cis-element required for SOS1 mRNA instability resides in the 500-bp region within the 2.2 kb at the 3¢ end of the SOS1 mRNA. Furthermore, mutations in the SOS1 gene render SOS1 mutants more tolerant to paraquat, a non-selective herbicide causing oxidative stress, indicating that SOS1 plays negative roles in tolerance of oxidative stress. A hypothetical model for the signaling pathway involving SOS1-mediated pH changes, NADPH oxidase activation, apoplastic ROS production and downstream signaling transduction is proposed, and the biological significance of ROS-mediated induction of SOS1 mRNA stability is discussed.
Huazhong Shi - One of the best experts on this subject based on the ideXlab platform.
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the plasma membrane polyamine transporter put3 is regulated by the na h antiporter SOS1 and protein kinase sos2
New Phytologist, 2020Co-Authors: Jian-kang Zhu, Haoxi Chai, Jianfei Guo, Yingli Zhong, Chuan-chih Hsu, Changsong Zou, Pengcheng Wang, Huazhong ShiAbstract:In Arabidopsis, the plasma membrane transporter PUT3 is important to maintain the cellular homeostasis of polyamines and plays a role in stabilizing mRNAs of some heat-inducible genes. The plasma membrane Na+ /H+ transporter SOS1 and the protein kinase SOS2 are two salt-tolerance determinants crucial for maintaining intracellular Na+ and K+ homeostasis. Here, we report that PUT3 genetically and physically interacts with SOS1 and SOS2, and these interactions modulate PUT3 transport activity. Overexpression of PUT3 (PUT3OE) results in hypersensitivity of the transgenic plants to polyamine and paraquat. The hypersensitivity of PUT3OE is inhibited by the SOS1 and sos2 mutations, which indicates that SOS1 and SOS2 are required for PUT3 transport activity. A protein interaction assay revealed that PUT3 physically interacts with SOS1 and SOS2 in yeast and plant cells. SOS2 phosphorylates PUT3 both in vitro and in vivo. SOS1 and SOS2 synergistically activate the polyamine transport activity of PUT3, and PUT3 also modulates SOS1 activity by activating SOS2 in yeast cells. Overall, our findings suggest that both plasma-membrane proteins PUT3 and SOS1 could form a complex with the protein kinase SOS2 in response to stress conditions and modulate the transport activity of each other through protein interactions and phosphorylation.
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The plasma-membrane polyamine transporter PUT3 is regulated by the Na+ /H+ antiporter SOS1 and protein kinase SOS2.
The New phytologist, 2020Co-Authors: Haoxi Chai, Jian-kang Zhu, Jianfei Guo, Yingli Zhong, Chuan-chih Hsu, Changsong Zou, Pengcheng Wang, Huazhong ShiAbstract:In Arabidopsis, the plasma membrane transporter PUT3 is important to maintain the cellular homeostasis of polyamines and plays a role in stabilizing mRNAs of some heat-inducible genes. The plasma membrane Na+ /H+ transporter SOS1 and the protein kinase SOS2 are two salt-tolerance determinants crucial for maintaining intracellular Na+ and K+ homeostasis. Here, we report that PUT3 genetically and physically interacts with SOS1 and SOS2, and these interactions modulate PUT3 transport activity. Overexpression of PUT3 (PUT3OE) results in hypersensitivity of the transgenic plants to polyamine and paraquat. The hypersensitivity of PUT3OE is inhibited by the SOS1 and sos2 mutations, which indicates that SOS1 and SOS2 are required for PUT3 transport activity. A protein interaction assay revealed that PUT3 physically interacts with SOS1 and SOS2 in yeast and plant cells. SOS2 phosphorylates PUT3 both in vitro and in vivo. SOS1 and SOS2 synergistically activate the polyamine transport activity of PUT3, and PUT3 also modulates SOS1 activity by activating SOS2 in yeast cells. Overall, our findings suggest that both plasma-membrane proteins PUT3 and SOS1 could form a complex with the protein kinase SOS2 in response to stress conditions and modulate the transport activity of each other through protein interactions and phosphorylation.
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Signaling control of SOS1 mRNA stability
Plant signaling & behavior, 2008Co-Authors: Jiafu Jiang, Huazhong ShiAbstract:Regulation of mRNA decay rates appears to be an important control point in determining the abundance of gene transcripts. Rapid change in decay rates of mRNAs could provide prompt responses of the plants to environmental fluctuations. SOS1 is a plasma-membrane Na+/H+ antiporter crucial for salt tolerance in Arabidopsis. In our recent paper in The Plant Journal, we have shown that SOS1 mRNA is inherently instable at normal growth conditions, but its stability is substantially elevated by salt and oxidative stress treatments. Salt stress-induced SOS1 mRNA stability is mediated by reactive oxygen species (ROS) produced, at least in part, through NADPH oxidases. We proposed a hypothetical model for the signaling pathway controlling SOS1 mRNA stability. In this addendum, we discuss the possible involvement of other components in conferring inherent instability and stress-induced stability of SOS1 mRNA.
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reactive oxygen species mediate na induced SOS1 mrna stability in arabidopsis
Plant Journal, 2007Co-Authors: Jung-sung Chung, Jian-kang Zhu, Ray A. Bressan, Paul M. Hasegawa, Huazhong ShiAbstract:*Summary Salt Overly Sensitive 1 (SOS1), a plasma membrane Na+ /H + antiporter in Arabidopsis, is a salt tolerance determinant crucial for the maintenance of ion homeostasis in saline stress conditions. SOS1 mRNA is unstable at normal growth conditions, but its stability is substantially increased under salt stress and other ionic and dehydration stresses. In addition, H 2O2 treatment increases the stability of SOS1 mRNA. SOS1 mRNA is inherently unstable and rapidly degraded with a half-life of approximately 10 min. Rapid decay of SOS1 mRNA requires new protein synthesis. Stress-induced SOS1 mRNA stability is mediated by reactive oxygen species (ROS). NADPH oxidase is also involved in the upregulation of SOS1 mRNA stability, presumably through the control of extracellular ROS production. The cis-element required for SOS1 mRNA instability resides in the 500-bp region within the 2.2 kb at the 3¢ end of the SOS1 mRNA. Furthermore, mutations in the SOS1 gene render SOS1 mutants more tolerant to paraquat, a non-selective herbicide causing oxidative stress, indicating that SOS1 plays negative roles in tolerance of oxidative stress. A hypothetical model for the signaling pathway involving SOS1-mediated pH changes, NADPH oxidase activation, apoplastic ROS production and downstream signaling transduction is proposed, and the biological significance of ROS-mediated induction of SOS1 mRNA stability is discussed.
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Reactive oxygen species mediate Na+-induced SOS1 mRNA stability in Arabidopsis
The Plant journal : for cell and molecular biology, 2007Co-Authors: Jung-sung Chung, Jian-kang Zhu, Ray A. Bressan, Paul M. Hasegawa, Huazhong ShiAbstract:*Summary Salt Overly Sensitive 1 (SOS1), a plasma membrane Na+ /H + antiporter in Arabidopsis, is a salt tolerance determinant crucial for the maintenance of ion homeostasis in saline stress conditions. SOS1 mRNA is unstable at normal growth conditions, but its stability is substantially increased under salt stress and other ionic and dehydration stresses. In addition, H 2O2 treatment increases the stability of SOS1 mRNA. SOS1 mRNA is inherently unstable and rapidly degraded with a half-life of approximately 10 min. Rapid decay of SOS1 mRNA requires new protein synthesis. Stress-induced SOS1 mRNA stability is mediated by reactive oxygen species (ROS). NADPH oxidase is also involved in the upregulation of SOS1 mRNA stability, presumably through the control of extracellular ROS production. The cis-element required for SOS1 mRNA instability resides in the 500-bp region within the 2.2 kb at the 3¢ end of the SOS1 mRNA. Furthermore, mutations in the SOS1 gene render SOS1 mutants more tolerant to paraquat, a non-selective herbicide causing oxidative stress, indicating that SOS1 plays negative roles in tolerance of oxidative stress. A hypothetical model for the signaling pathway involving SOS1-mediated pH changes, NADPH oxidase activation, apoplastic ROS production and downstream signaling transduction is proposed, and the biological significance of ROS-mediated induction of SOS1 mRNA stability is discussed.
Eugenio Santos - One of the best experts on this subject based on the ideXlab platform.
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The CSN3 subunit of the COP9 signalosome interacts with the HD region of SOS1 regulating stability of this GEF protein
Oncogenesis, 2019Co-Authors: Natasha Zarich, José Luis Oliva, Begoña Anta, Alberto Fernández-medarde, Alicia Ballester, María Pilar Lucas, Ana Belén Cámara, José M. Rojas-cabañeros, Eugenio SantosAbstract:SOS1 is an universal, widely expressed Ras guanine nucleotide-exchange factor (RasGEF) in eukaryotic cells. Its N-terminal HD motif is known to be involved in allosteric regulation of SOS1 GEF activity through intramolecular interaction with the neighboring PH domain. Here, we searched for other cellular proteins also able to interact productively with the SOS1 HD domain. Using a yeast two-hybrid system, we identified the interaction between the SOS1 HD region and CSN3, the third component of the COP9 signalosome, a conserved, multi-subunit protein complex that functions in the ubiquitin–proteasome pathway to control degradation of many cellular proteins. The interaction of CSN3 with the HD of SOS1 was confirmed in vitro by GST pull-down assays using truncated mutants and reproduced in vivo by co-immunoprecipitation with the endogenous, full-length cellular SOS1 protein . In vitro kinase assays showed that PKD, a COP9 signalosome-associated-kinase, is able to phosphorylate SOS1. The intracellular levels of SOS1 protein were clearly diminished following CSN3 or PKD knockdown. A sizable fraction of the endogenous SOS1 protein was found ubiquitinated in different mammalian cell types. A significant reduction of RasGTP formation upon growth factor stimulation was also observed in CSN3-silenced as compared with control cells. Our data suggest that the interaction of SOS1 with the COP9 signalosome and PKD plays a significant role in maintenance of cellular SOS1 protein stability and homeostasis under physiological conditions and raises the possibility of considering the CSN/PKD complex as a potential target for design of novel therapeutic drugs.
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PO-187 Defective liver regeneration ability of SOS1-KO and SOS1/2-DKO, but not Sos2-KO mice
ESMO Open, 2018Co-Authors: C. Gómez, Alberto Fernández-medarde, J Vaquero, Rósula García-navas, Rocío Fuentes-mateos, Fernando C. Baltanás, David Jimeno, Nuria Calzada, Eugenio SantosAbstract:Introduction To ascertain specific functional role(s) of the SOS1 and Sos2 Ras-GEF activators we investigated phenotypic effects of single or combined disruption of SOS1 and/or Sos2 in adult mice by using a tamoxifen-inducible SOS1-KO system. Upon TAM induction, the resulting SOS1/2-DKO animals die precipitously (in about 2 weeks) whereas single SOS1-KO or Sos2-KO adult mice are perfectly viable. Histological examination of DKO mice showed that the internal organs most severely affected by concomitant SOS1 and Sos2 loss include the liver and gallbladder in the gastrointestinal (GI) tract. Material and methods To determine cause(s) of the quick death of SOS1/2-DKO mice, we analysed blood and GI tissues from 6–8 week-old mice of 4 relevant Sos genotypes (WT, SOS1-KO, Sos2-KO and SOS1/2-DKO) similarly treated with TAM for 13 days. Different biochemical parameters were quantitated in blood serum and liver samples, and various IHC assays were also performed on different organs of the GI tract. Liver regeneration was characterised by means of partial hepatectomy studies of WT, SOS1-KO and Sos2-KO animals previously treated with TAM for 10 days. Results and discussions Combined loss of SOS1 and Sos2 in DKO mice resulted in markedly reduced levels of total serum protein and increased serum levels of lactate dehydrogenase, creatinine kinase and other liver enzymes, suggesting the occurrence of substantial liver failure in these animals. Histological analysis of the DKO animals showed a quick overall structural degeneration of the liver accompanied by increased levels of oxidative stress in the hepatic lobules. We also observed marked distension of the gallbladder, perhaps linked to decreased CCK levels in the gut mucosa cells. The dilatation of the gallbladder together with the observed decrease of serum triglycerides and fat in all the organs analysed point to significant impairment of the lipidic metabolism in SOS1/2-DKO mice. Finally, our partial hepatectomy studies in single Sos KO mice showed that hepatic regeneration critically depends on the presence of SOS1, whereas Sos2 appears to be dispensable for this process of organ recovery after liver damage. Conclusion Our data suggest functional redundancy of SOS1 and Sos2 for overall homeostasis of GI organs, especially liver and gallbladder. Our studies also show that SOS1, but not Sos2, is the main, critical RasGEF required for liver regeneration and tissue repair upon organ injury. Supported by AECC, PI16/0213, PI19/01083, CB16/12/00352 (ISCIII) and SA043U16 (CyL-FEDER) Spain
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PO-173 Critical requirement of the SOS1 and Sos2 RasGEFs for maintenance of mitochondrial homeostasis
ESMO Open, 2018Co-Authors: R García Navas, P. Liceras-boillos, C Lillo, C Nuevo-tapioles, B. Anta, C Gómez Rodríguez, Eugenio SantosAbstract:Introduction The homologous, ubiquitously expressed, members (SOS1 and Sos2) of the Sos family of RasGEFs participate in multiple signalling pathways but their specific cellular functions are not clearly defined yet. Material and methods Using a tamoxifen (4OHT)-inducible, conditional SOS1 null mutation, here we generated and analysed wild type (WT), single SOS1-KO, constitutive Sos2-KO and double SOS1/2-DKO primary mouse embryonic fibroblasts (MEFs) in an effort to ascertain the functional specificity or redundancy of SOS1 and Sos2 at the cellular level. Results and discussions SOS1-KO and SOS1/2-DKO MEFs exhibited distinct flat morphology, enlarged cell perimeter and altered cytoskeletal organisation that were not observed in WT and Sos2 KO counterparts. SOS1-KO and SOS1/2-DKO MEFs also displayed significant accumulation of cytoplasmic bodies identified as autophagosomes containing degraded mitochondria by means of electron microscopy and specific markers. Consistent with a mitophagic phenotype, in vivo labelling using specific fluorophores revealed increased levels of mitochondrial oxidative stress in the SOS1-KO and the SOS1/2-DKO cells as compared to Sos2-KO or WT MEFs. Treatment of the MEF cultures with antioxidants such as GSH and NAC corrected the altered perimeter size and proliferative rate of SOS1-KO and SOS1/2-DKO MEFs to levels similar to those of WT and Sos2-KO, but not recover oxidative stress. Furthermore, treatment with the specific mitochondrial superoxide scavenger mitoTEMPO recovered endogenous redox-homeostasis in SOS1-KO and SOS1/2-DKO to normal levels. Analysis of MEFs concomitantly loaded with MitoTracker Green (Δψ-independent) and MitoTracker Red (Δψ-dependent) showed a significantly increased of dysfunctional mitochondria in the SOS1/2-DKO MEFs in comparison to all other genotypes. Finally, Seahorse-based measurements of mitochondrial parameters showed that basal and maximal mitochondrial respiration, spare respiratory capacity, and ATP production, were also significantly decreased in SOS1/2-DKO cells as compared to MEFs of all the other genotypes. Conclusion Our data uncover a direct mechanistic link between Sos RasGEF proteins and the control of mitochondrial oxidative stress and respiration. Dysfunctional mitochondria are a key element in a variety of serious diseases, including cancer, and thus a promising therapeutic target. This work was supported by grants PI16/02137 (FIS) and CIBERONC (ONCG19//2017) from ISCIII; SA043U16 from FEDER-JCyL; FS/35–2017 from FSB and AECC, Spain.
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Functional Redundancy of SOS1 and Sos2 for Lymphopoiesis and Organismal Homeostasis and Survival
Molecular and cellular biology, 2013Co-Authors: Fernando C. Baltanás, David Jimeno, Martin Perez-andres, A. Ginel-picardo, David Díaz, P. Liceras-boillos, Robert L. Kortum, Lawrence E. Samelson, Alberto Orfao, Eugenio SantosAbstract:SOS1 and Sos2 are ubiquitously expressed, universal Ras guanine nucleotide exchange factors (Ras-GEFs) acting in multiple signal transduction pathways activated by upstream cellular kinases. The embryonic lethality of SOS1 null mutants has hampered ascertaining the specific in vivo contributions of SOS1 and Sos2 to processes controlling adult organism survival or development of hematopoietic and nonhematopoietic organs, tissues, and cell lineages. Here, we generated a tamoxifen-inducible SOS1-null mouse strain allowing analysis of the combined disruption of SOS1 and Sos2 (SOS1/2) during adulthood. SOS1/2 double-knockout (DKO) animals died precipitously, whereas individual SOS1 and Sos2 knockout (KO) mice were perfectly viable. A reduced percentage of total bone marrow precursors occurred in single-KO animals, but a dramatic depletion of B-cell progenitors was specifically detected in SOS1/2 DKO mice. We also confirmed a dominant role of SOS1 over Sos2 in early thymocyte maturation, with almost complete thymus disappearance and dramatically higher reduction of absolute thymocyte counts in SOS1/2 DKO animals. Absolute counts of mature B and T cells in spleen and peripheral blood were unchanged in single-KO mutants, while significantly reduced in SOS1/2 DKO mice. Our data demonstrate functional redundancy between SOS1 and Sos2 for homeostasis and survival of the full organism and for development and maturation of T and B lymphocytes.
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Mammalian son of sevenless Guanine nucleotide exchange factors: old concepts and new perspectives.
Genes & cancer, 2011Co-Authors: José M. Rojas, José Luis Oliva, Eugenio SantosAbstract:The Son of Sevenless (Sos) factors were originally discovered 2 decades ago as specialized Ras activators in signaling pathways controlling the process of R7 cell development in the eye of Drosophila melanogaster. The 2 known members of the mammalian Sos family (SOS1 and Sos2) code for ubiquitously expressed, highly homologous (69% overall) proteins involved in coupling signals originated by cell surface receptor tyrosine kinases (RTKs) to downstream, Ras-dependent mitogenic signaling pathways. Mechanistically, the Sos proteins function as enzymatic factors interacting with Ras proteins in response to upstream stimuli to promote guanine nucleotide exchange (GDP/GTP) and subsequent formation of the active Ras-GTP complex. In this review, we summarize current knowledge on structural, regulatory, and functional aspects of the Sos family, focusing on specific aspects of Sos biology such as structure-function relationship, crosstalk with different signaling pathways, and in vivo functional significance as deduced from phenotypic characterization of Sos knockout mice and human genetic syndromes caused by germline hSOS1 mutations.
Zed Rengel - One of the best experts on this subject based on the ideXlab platform.
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na h antiporter activity of the SOS1 gene lifetime imaging analysis and electrophysiological studies on arabidopsis seedlings
Physiologia Plantarum, 2009Co-Authors: Kun-mei Guo, Olga Babourina, Zed RengelAbstract:Based on sequence analysis, the salt overly sensitive (SOS1) gene has been suggested to function as a Na(+)/H(+) antiporter located at the plasma membrane of plant cells, being expressed mostly in the meristem zone of the root and in the parenchyma cells surrounding the vascular tissue of the stem. In this study, we compared net H(+) and Ca(2+) fluxes and intracellular pH and [Ca(2+)](cyt) in the root meristem zone of Arabidopsis wild-type (WT) and sos mutants before and after salt stress. In addition, we studied the effect of pretreatment with amiloride (an inhibitor of Na(+)/H(+) antiporters) on net ion fluxes, intracellular pH and intracellular Ca(2+) activity ([Ca(2+)](cyt)) in WT plants and SOS1 mutants before and after salt stress. Net ion fluxes were measured using microelectrode ion flux estimation (MIFE) and intracellular pH and [Ca(2+)](cyt) using fluorescence lifetime imaging microscopy (FLIM) techniques. During the first 15 min after NaCl application, SOS1 mutants showed net H(+) efflux and intracellular alkalinization in the meristem zone, whereas sos2 and sos3 mutants and WT showed net H(+) influx and slight intracellular acidification in the meristem zone. Treatment with amiloride led to intracellular acidification and lower net H(+) flux in WT plants and to a decrease in intracellular Ca(2+) in WT and SOS1 plants. WT plants pretreated with amiloride did not show positive net H(+) flux and intracellular acidification. After NaCl application, internal pH shifted to higher values in WT and SOS1 plants. However, absolute values of H(+) fluxes were higher and internal pH values were lower in WT plants pretreated with amiloride compared with SOS1 mutants. Therefore, the SOS1 transporter is involved in H(+) influx into the meristem zone of Arabidopsis roots, or it may function as a Na(+)/H(+) antiporter. Amiloride affects SOS1 and other Na(+)/H(+) antiporters in plant cells because of its ability to decrease the H(+) gradient across the plasma membrane.
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Na(+)/H(+) antiporter activity of the SOS1 gene: lifetime imaging analysis and electrophysiological studies on Arabidopsis seedlings.
Physiologia plantarum, 2009Co-Authors: Kun-mei Guo, Olga Babourina, Zed RengelAbstract:Based on sequence analysis, the salt overly sensitive (SOS1) gene has been suggested to function as a Na(+)/H(+) antiporter located at the plasma membrane of plant cells, being expressed mostly in the meristem zone of the root and in the parenchyma cells surrounding the vascular tissue of the stem. In this study, we compared net H(+) and Ca(2+) fluxes and intracellular pH and [Ca(2+)](cyt) in the root meristem zone of Arabidopsis wild-type (WT) and sos mutants before and after salt stress. In addition, we studied the effect of pretreatment with amiloride (an inhibitor of Na(+)/H(+) antiporters) on net ion fluxes, intracellular pH and intracellular Ca(2+) activity ([Ca(2+)](cyt)) in WT plants and SOS1 mutants before and after salt stress. Net ion fluxes were measured using microelectrode ion flux estimation (MIFE) and intracellular pH and [Ca(2+)](cyt) using fluorescence lifetime imaging microscopy (FLIM) techniques. During the first 15 min after NaCl application, SOS1 mutants showed net H(+) efflux and intracellular alkalinization in the meristem zone, whereas sos2 and sos3 mutants and WT showed net H(+) influx and slight intracellular acidification in the meristem zone. Treatment with amiloride led to intracellular acidification and lower net H(+) flux in WT plants and to a decrease in intracellular Ca(2+) in WT and SOS1 plants. WT plants pretreated with amiloride did not show positive net H(+) flux and intracellular acidification. After NaCl application, internal pH shifted to higher values in WT and SOS1 plants. However, absolute values of H(+) fluxes were higher and internal pH values were lower in WT plants pretreated with amiloride compared with SOS1 mutants. Therefore, the SOS1 transporter is involved in H(+) influx into the meristem zone of Arabidopsis roots, or it may function as a Na(+)/H(+) antiporter. Amiloride affects SOS1 and other Na(+)/H(+) antiporters in plant cells because of its ability to decrease the H(+) gradient across the plasma membrane.
Eui Ju Choi - One of the best experts on this subject based on the ideXlab platform.
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CIIA negatively regulates the Ras–Erk1/2 signaling pathway through inhibiting the Ras-specific GEF activity of SOS1
Journal of Cell Science, 2014Co-Authors: Hyun Sub Hwang, Sang Gil Hwang, Kyoung Wan Yoon, Je Hyun Yoon, Kyung Hye Roh, Eui Ju ChoiAbstract:Son of sevenless 1 (SOS1) is a Ras-specific guanine-nucleotide-exchange factor (GEF) that mediates intracellular signaling processes induced by receptor tyrosine kinases. In this study, we show that CIIA (also known as VPS28) physically associates with SOS1 and thereby inhibits the GEF activity of SOS1 on Ras, which prevents the epidermal growth factor (EGF)-induced activation of the Ras-Erk1/2 pathway. Furthermore, CIIA inhibited cyclin D1 expression, as well as DNA, synthesis in response to EGF. Intriguingly, CIIA failed to inhibit the Ras-specific GEF activity of Noonan-syndrome-associated SOS1 mutants (M269R, R552G, W729L and E846K). Taken together, our results suggest that CIIA functions as a negative modulator of the SOS1-Ras signaling events initiated by peptide growth factors including EGF.
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CIIA negatively regulates the Ras-Erk1/2 signaling pathway through inhibiting the Ras-specific GEF activity of SOS1.
Journal of cell science, 2014Co-Authors: Hyun Sub Hwang, Sang Gil Hwang, Kyoung Wan Yoon, Je Hyun Yoon, Kyung Hye Roh, Eui Ju ChoiAbstract:Son of sevenless 1 (SOS1) is a Ras-specific guanine-nucleotide-exchange factor (GEF) that mediates intracellular signaling processes induced by receptor tyrosine kinases. In this study, we show that CIIA (also known as VPS28) physically associates with SOS1 and thereby inhibits the GEF activity of SOS1 on Ras, which prevents the epidermal growth factor (EGF)-induced activation of the Ras-Erk1/2 pathway. Furthermore, CIIA inhibited cyclin D1 expression, as well as DNA, synthesis in response to EGF. Intriguingly, CIIA failed to inhibit the Ras-specific GEF activity of Noonan-syndrome-associated SOS1 mutants (M269R, R552G, W729L and E846K). Taken together, our results suggest that CIIA functions as a negative modulator of the SOS1-Ras signaling events initiated by peptide growth factors including EGF.
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CIIA functions as a molecular switch for the Rac1-specific GEF activity of SOS1
The Journal of cell biology, 2011Co-Authors: Hyun Sub Hwang, Sang Gil Hwang, Kyoung Wan Yoon, Jun Ho Cho, Ji Soo Chae, Ssang-goo Cho, Eui Ju ChoiAbstract:Son of sevenless 1 (SOS1) is a dual guanine nucleotide exchange factor (GEF) that activates the guanosine triphosphatases Rac1 and Ras, which mediate signaling initiated by peptide growth factors. In this paper, we show that CIIA is a new binding partner of SOS1. CIIA promoted the SOS1–Rac1 interaction and inhibited the SOS1–Ras interaction. Furthermore, CIIA promoted the formation of an SOS1–EPS8 complex and SOS1-mediated Rac1 activation, whereas it inhibited SOS1-mediated activation of Ras. Transforming growth factor β (TGF-β) up-regulated the expression of CIIA and thereby promoted the association between CIIA and SOS1 in A549 human lung adenocarcinoma cells. Depletion of CIIA in these cells by ribonucleic acid interference inhibited the TGF-β–induced interaction between SOS1 and EPS8, activation of Rac1, and cell migration. Together, these results suggest that CIIA mediates the TGF-β–induced activation of SOS1–Rac1 signaling and cell migration in A549 cells. They further show that CIIA functions as a molecular switch for the GEF activity of SOS1, directing this activity toward Rac1.