Genomes and Genes
Gene Symbol: Sos1
Description: SOS Ras/Rac guanine nucleotide exchange factor 1
Alias: 4430401P03Rik, 9630010N06, AI449023, son of sevenless homolog 1, guanine nucleotide releasing factor, ras guanine exchange factor, son-of-sevenless 1
- Suzuki T, Mitake S, Murata S. Presence of up-stream and downstream components of a mitogen-activated protein kinase pathway in the PSD of the rat forebrain. Brain Res. 1999;840:36-44 pubmed..We found that RSK1, Sos1, N-Shc 66 kDa, N-Shc 52 kDa, and Grb2 were present in the PSD fraction, and cPLA(2) was present in the synaptic ..
- Xue Y, Yuwen T, Zhu F, Skrynnikov N. Role of electrostatic interactions in binding of peptides and intrinsically disordered proteins to their folded targets. 1. NMR and MD characterization of the complex between the c-Crk N-SH3 domain and the peptide Sos. Biochemistry. 2014;53:6473-95 pubmed publisher..The results of the combined NMR and MD study of this engineered system will be reported in the next part of this paper. ..
- Oliver G, Mailhos A, Wehr R, Copeland N, Jenkins N, Gruss P. Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development. 1995;121:4045-55 pubmed..This region shares a homology with the distal region of mouse chromosome 17 where Six3 has been mapped. ..
- Kortum R, Rouquette Jazdanian A, Miyaji M, Merrill R, Markegard E, Pinski J, et al. A phospholipase C-Î³1-independent, RasGRP1-ERK-dependent pathway drives lymphoproliferative disease in linker for activation of T cells-Y136F mutant mice. J Immunol. 2013;190:147-58 pubmed publisher..binding and activation, genetic analysis revealed RasGRP1, and not Sos1 or Sos2, to be the major Ras guanine exchange factor responsible for ERK activation and the lymphoproliferative phenotype in these mice...
- Nielsen K, Papageorge A, Vass W, Willumsen B, Lowy D. The Ras-specific exchange factors mouse Sos1 (mSos1) and mSos2 are regulated differently: mSos2 contains ubiquitination signals absent in mSos1. Mol Cell Biol. 1997;17:7132-8 pubmedWe have compared aspects of the mouse sos1 (msos1) and msos2 genes, which encode widely expressed, closely related Ras-specific exchange factors...
- Webb G, Jenkins N, Largaespada D, Copeland N, Fernandez C, Bowtell D. Mammalian homologues of the Drosophila Son of sevenless gene map to murine chromosomes 17 and 12 and to human chromosomes 2 and 14, respectively. Genomics. 1993;18:14-9 pubmed..We recently cloned two mammalian genes, Son of sevenless 1 (mSos1) and Son of sevenless 2 (mSos2), whose protein products appear to be important positive regulators of ..
- Guittard G, Kortum R, Balagopalan L, Ã‡uburu N, Nguyen P, Sommers C, et al. Absence of both Sos-1 and Sos-2 in peripheral CD4(+) TÂ cells leads to PI3K pathway activation and defects in migration. Eur J Immunol. 2015;45:2389-95 pubmed publisher..The increased activity of the PI3K/AKT pathway led to downregulation of the surface receptor CD62L in Sos-1/2dKO T cells and a subsequent impairment in T-cell migration. ..
- Ferreon J, Ferreon A, Li K, Lemon S. Molecular determinants of TRIF proteolysis mediated by the hepatitis C virus NS3/4A protease. J Biol Chem. 2005;280:20483-92 pubmed..Because SH3 binding motifs are also present in NS5A, a viral protein that interacts with NS3, we speculate that the NS3 3(10) helix may be a site of interaction with other viral proteins. ..
- Hoeppner M, Gilbert D, Copeland N, Jenkins N, Linzer D, Wu B. Cloning and characterization of mouse CCAAT binding factor. Nucleic Acids Res. 1996;24:1091-8 pubmed..Co-expression of these two forms influences their localization, however, indicating that CBF activity can be regulated by the relative amounts of the two forms expressed in a cell. ..
- Kortum R, Balagopalan L, Alexander C, Garcia J, Pinski J, Merrill R, et al. The ability of Sos1 to oligomerize the adaptor protein LAT is separable from its guanine nucleotide exchange activity in vivo. Sci Signal. 2013;6:ra99 pubmed publisher..The activation of the small guanosine triphosphatase Ras by the guanine nucleotide exchange factor (GEF) Sos1 (Son of Sevenless 1) is a central feature of many receptor-stimulated signaling pathways...
- Yulug I, Egan S, Pollock P, Fisher E. A homologue of the Drosophila Son of sevenless gene maps to mouse chromosome 17. Genomics. 1993;18:733-4 pubmed
- Lesourne R, Zvezdova E, Song K, El Khoury D, Uehara S, Barr V, et al. Interchangeability of Themis1 and Themis2 in thymocyte development reveals two related proteins with conserved molecular function. J Immunol. 2012;189:1154-61 pubmed publisher..These results suggest that conserved molecular features of the Themis1 and Themis2 proteins are important for their biological activity and predict that Themis1 and Themis2 may perform similar functions in T and B cells, respectively. ..
- Wilhelmsen K, Copp J, Glenn G, Hoffman R, Tucker P, van der Geer P. Purification and identification of protein-tyrosine kinase-binding proteins using synthetic phosphopeptides as affinity reagents. Mol Cell Proteomics. 2004;3:887-95 pubmed..Novel protein-protein interactions may provide useful targets for the development of drugs that interfere with the activation of signaling cascades used by protein-tyrosine kinases to turn on cell division. ..
- Ferguson M, Fan X, Mukherjee M, Luo J, Khan R, Ferreon J, et al. Directed discovery of bivalent peptide ligands to an SH3 domain. Protein Sci. 2004;13:626-32 pubmed..PP-G(4)-L may aid in the discovery of additional binding partners of Grb2 family SH3 domains. ..
- Rozakis Adcock M, Fernley R, Wade J, Pawson T, Bowtell D. The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1. Nature. 1993;363:83-5 pubmed..EGF stimulation induces binding of the Grb2-mSos1 complex to the autophosphorylated EGF receptor, and mSos1 phosphorylation. Grb2 therefore appears to link tyrosine kinases to a Ras-GNRP in mammalian cells. ..
- Rozakis Adcock M, van der Geer P, Mbamalu G, Pawson T. MAP kinase phosphorylation of mSos1 promotes dissociation of mSos1-Shc and mSos1-EGF receptor complexes. Oncogene. 1995;11:1417-26 pubmed..These findings suggest a potential inhibitory role for MAP-kinase in attenuating nucleotide exchange on Ras, by uncoupling mSos1 from membrane-bound receptor complexes that lead to Ras activation. ..
- Kortum R, Sommers C, Pinski J, Alexander C, Merrill R, Li W, et al. Deconstructing Ras signaling in the thymus. Mol Cell Biol. 2012;32:2748-59 pubmed publisher..Recent studies have shown a role for the Ras guanine exchange factor (RasGEF) Sos1 at the pre-TCR checkpoint...
- Aoki K, Nakamura T, Fujikawa K, Matsuda M. Local phosphatidylinositol 3,4,5-trisphosphate accumulation recruits Vav2 and Vav3 to activate Rac1/Cdc42 and initiate neurite outgrowth in nerve growth factor-stimulated PC12 cells. Mol Biol Cell. 2005;16:2207-17 pubmed..These observations demonstrated for the first time that Vav2 and Vav3 are essential constituents of the positive feedback loop that is comprised of PI3-kinase and Rac1/Cdc42 and cycles locally with morphological changes. ..
- Salojin K, Zhang J, Cameron M, Gill B, Arreaza G, Ochi A, et al. Impaired plasma membrane targeting of Grb2-murine son of sevenless (mSOS) complex and differential activation of the Fyn-T cell receptor (TCR)-zeta-Cbl pathway mediate T cell hyporesponsiveness in autoimmune nonobese diabetic mice. J Exp Med. 1997;186:887-97 pubmed..These findings implicate mSOS as an important mediator of downregulation of Ras signaling in hyporesponsive NOD T cells. ..
- Heaney C, Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S, et al. Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation. Blood. 1997;89:297-306 pubmed..Thus, a direct interaction of CRKL and BCR-ABL is not required for CRKL to become tyrosine phosphorylated by BCR-ABL and suggests that CRKL function may still be required for BCR-ABL function through an indirect interaction. ..
- Baruzzi A, Remelli S, Lorenzetto E, Sega M, Chignola R, Berton G. Sos1 Regulates Macrophage Podosome Assembly and Macrophage Invasive Capacity. J Immunol. 2015;195:4900-12 pubmed publisher..Considering that Abl has been reported to phosphorylate the guanine nucleotide exchange factor Sos1, eliciting its Rac-guanine nucleotide exchange factor activity, and Rac regulates podosome formation in myeloid ..
- Halupa A, Chohan M, Stickle N, Beattie B, Miller B, Barber D. Erythropoietin receptor Y479 couples to ERK1/2 activation via recruitment of phospholipase Cgamma. Exp Cell Res. 2005;309:1-11 pubmed..Hence, we have identified a novel adapter function for PLCgamma1 in EPO signaling in which recruitment of PLCgamma1 to EPO-R may lead to activation of the ERK pathway. ..
- Shiraishi K, Ascoli M. Activation of the lutropin/choriogonadotropin receptor in MA-10 cells stimulates tyrosine kinase cascades that activate ras and the extracellular signal regulated kinases (ERK1/2). Endocrinology. 2006;147:3419-27 pubmed..We conclude that the SFKs are responsible for the LHR-mediated phosphorylation of the EGFR and Shc, the formation of complexes containing Shc and Sos, the activation of Ras, and the phosphorylation of ERK1/2. ..
- Hartman Z, Zhao H, Agazie Y. HER2 stabilizes EGFR and itself by altering autophosphorylation patterns in a manner that overcomes regulatory mechanisms and promotes proliferative and transformation signaling. Oncogene. 2013;32:4169-80 pubmed publisher..These results imply that complementing HER2-targeted therapies with anti-EGFR drugs may be beneficial in HER2-positive breast cancer. ..
- Xu X, Yi T, Tang B, Lambeth J. Disabled-2 (Dab2) is an SH3 domain-binding partner of Grb2. Oncogene. 1998;16:1561-9 pubmed..These data indicate that Dab2 binds to the SH3 domains of Grb2 via its C-terminal proline-rich sequences. Dab2 may modulate growth factor/Ras pathways by competing with Sos for binding to Grb2. ..
- Sala V, Gallo S, Leo C, Gatti S, Gelb B, Crepaldi T. Signaling to cardiac hypertrophy: insights from human and mouse RASopathies. Mol Med. 2012;18:938-47 pubmed publisher..Future research promises to further elucidate the complex molecular interactions responsible for cardiac hypertrophy, possibly pointing the way for the identification of new specific targets for the treatment of HCM. ..
- Innocenti M, Frittoli E, Ponzanelli I, Falck J, Brachmann S, Di Fiore P, et al. Phosphoinositide 3-kinase activates Rac by entering in a complex with Eps8, Abi1, and Sos-1. J Cell Biol. 2003;160:17-23 pubmed..Our results define a mechanism whereby propagation of signals, originating from RTKs or Ras and leading to actin reorganization, is controlled by direct physical interaction between PI3K and a Rac-specific GEF complex. ..
- Miura K, Miyazawa S, Furuta S, Mitsushita J, Kamijo K, Ishida H, et al. The Sos1-Rac1 signaling. Possible involvement of a vacuolar H(+)-ATPase E subunit. J Biol Chem. 2001;276:46276-83 pubmed..Thus, the data indicate that V-ATPase E may participate in the regulation of the mSos1-dependent Rac1 signaling pathway involved in growth factor receptor-mediated cell growth control. ..
- Schmutte C, Marinescu R, Copeland N, Jenkins N, Overhauser J, Fishel R. Refined chromosomal localization of the mismatch repair and hereditary nonpolyposis colorectal cancer genes hMSH2 and hMSH6. Cancer Res. 1998;58:5023-6 pubmed..These results clarify the position of the chromosome 2 hereditary nonpolyposis colorectal cancer locus, which was originally reported to be associated with an adjacent region (chromosome 2p14-16). ..
- Huang Z, Chen J, Regan J, Maguire C, Tang R, Dong X, et al. Loss of microRNAs in neural crest leads to cardiovascular syndromes resembling human congenital heart defects. Arterioscler Thromb Vasc Biol. 2010;30:2575-86 pubmed publisher..Our results uncovered a central role for Dicer and miRNAs in NCC survival, migration, and patterning in craniofacial and cardiovascular development which, when mutated, lead to congenital neuro-craniofacial-cardiac defects. ..
- Chen P, Wakimoto H, Conner D, Araki T, Yuan T, Roberts A, et al. Activation of multiple signaling pathways causes developmental defects in mice with a Noonan syndrome–associated Sos1 mutation. J Clin Invest. 2010;120:4353-65 pubmed publisher..About 10%-15% of individuals with NS have mutations in son of sevenless 1 (SOS1), which encodes a RAS and RAC guanine nucleotide exchange factor (GEF)...
- Qu Y, Chen Q, Lai X, Zhu C, Chen C, Zhao X, et al. SUMOylation of Grb2 enhances the ERK activity by increasing its binding with Sos1. Mol Cancer. 2014;13:95 pubmed publisher..receptor-bound protein 2) is a key adaptor protein in maintaining the ERK activity via linking Sos1 (Son of sevenless homolog 1) or other proteins to activated RTKs, such as EGFR...
- Liceras Boillos P, GarcÃa Navas R, Ginel Picardo A, Anta B, PÃ©rez AndrÃ©s M, Lillo C, et al. Sos1 disruption impairs cellular proliferation and viability through an increase in mitochondrial oxidative stress in primary MEFs. Oncogene. 2016;35:6389-6402 pubmed publisherUsing a 4-hydroxytamoxifen (4OHT)-inducible, conditional Sos1-null mutation, we analyzed wild-type (WT), single Sos1-KO, Sos2-KO and double Sos1/2 KO primary mouse embryonic fibroblasts (MEF) with an aim at evaluating the functional ..
- Houtman J, Yamaguchi H, Barda Saad M, Braiman A, Bowden B, Appella E, et al. Oligomerization of signaling complexes by the multipoint binding of GRB2 to both LAT and SOS1. Nat Struct Mol Biol. 2006;13:798-805 pubmed..tyrosines on the adaptor protein LAT and the GRB2 SH3 domains associate with the proline-rich regions of SOS1 and CBL...
- Oliver G, Wehr R, Jenkins N, Copeland N, Cheyette B, Hartenstein V, et al. Homeobox genes and connective tissue patterning. Development. 1995;121:693-705 pubmed..Six 1 and Six 2 also are expressed in skeletal and smooth muscle, respectively. These genes may participate in the patterning of the distal tendons of the limb phalanges by setting positional values along the limb axes. ..
- Wang D, Hammond V, Abud H, Bertoncello I, McAvoy J, Bowtell D. Mutation in Sos1 dominantly enhances a weak allele of the EGFR, demonstrating a requirement for Sos1 in EGFR signaling and development. Genes Dev. 1997;11:309-20 pubmedWe have investigated the role of the mammalian Son of sevenless 1 (Sos1) protein in growth factor signaling in vivo by generating mice and cell lines that lacked the Sos1 protein...
- Kouhara H, Hadari Y, Spivak Kroizman T, Schilling J, Bar Sagi D, Lax I, et al. A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway. Cell. 1997;89:693-702 pubmed..Finally, we demonstrate that FRS2 is closely related and probably indentical to SNT, the long-sought target of FGF and NGF receptors. ..
- Xie Y, Wang Y, Sun T, Wang F, Trostinskaia A, Puscheck E, et al. Six post-implantation lethal knockouts of genes for lipophilic MAPK pathway proteins are expressed in preimplantation mouse embryos and trophoblast stem cells. Mol Reprod Dev. 2005;71:1-11 pubmed..These included FRS2alpha, GAB1, GRB2, SOS1, Raf-B, and Raf1...
- Geissler K, Jung M, Riecken L, Sperka T, Cui Y, Schacke S, et al. Regulation of Son of sevenless by the membrane-actin linker protein ezrin. Proc Natl Acad Sci U S A. 2013;110:20587-92 pubmed publisher..We propose an additional essential step in SOS/Ras control that is relevant for human cancer as well as all physiological processes involving Ras. ..
- Yohannan J, Wienands J, Coggeshall K, Justement L. Analysis of tyrosine phosphorylation-dependent interactions between stimulatory effector proteins and the B cell co-receptor CD22. J Biol Chem. 1999;274:18769-76 pubmed..This finding suggests that PLCgamma and PI3K may be recruited to CD22 either through a direct interaction with Tyr863 or indirectly through an association with one or more intermediate proteins. ..
- Spencer M, Shao H, Tucker H, Andres D. Nerve growth factor-dependent activation of the small GTPase Rin. J Biol Chem. 2002;277:17605-15 pubmed..Together, these studies indicate that Rin activation is a direct downstream effect of growth factor-dependent signaling in neuronal cells and suggest that Rin may function to transduce signals within the mature nervous system. ..
- Kortum R, Sommers C, Alexander C, Pinski J, Li W, Grinberg A, et al. Targeted Sos1 deletion reveals its critical role in early T-cell development. Proc Natl Acad Sci U S A. 2011;108:12407-12 pubmed publisher..In thymocytes, Ras is activated by the Ras guanine exchange factors (RasGEFs) Sos1, Sos2, and RasGRP1...
- Reynolds L, de Bettignies C, Norton T, Beeser A, Chernoff J, Tybulewicz V. Vav1 transduces T cell receptor signals to the activation of the Ras/ERK pathway via LAT, Sos, and RasGRP1. J Biol Chem. 2004;279:18239-46 pubmed..Second, Vav1 is required for recruitment of Sos1 and -2 to the transmembrane adapter protein LAT...
- Chook Y, Gish G, Kay C, Pai E, Pawson T. The Grb2-mSos1 complex binds phosphopeptides with higher affinity than Grb2. J Biol Chem. 1996;271:30472-8 pubmed
- Gross I, Bassit B, Benezra M, Licht J. Mammalian sprouty proteins inhibit cell growth and differentiation by preventing ras activation. J Biol Chem. 2001;276:46460-8 pubmed..Sos complex to selectively uncouple growth factor signals from Ras activation and the MAP Kinase pathway. ..
- Anafi M, Kiefer F, Gish G, Mbamalu G, Iscove N, Pawson T. SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1. J Biol Chem. 1997;272:27804-11 pubmed..Such interaction may provide a possible mechanism for cross-talk between distinct biochemical pathways following the activation of tyrosine kinases. ..
- Baltanás F, Perez Andres M, Ginel Picardo A, Diaz D, Jimeno D, Liceras Boillos P, et al. Functional redundancy of Sos1 and Sos2 for lymphopoiesis and organismal homeostasis and survival. Mol Cell Biol. 2013;33:4562-78 pubmed publisherb>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...
- Kon Kozlowski M, Pani G, Pawson T, Siminovitch K. The tyrosine phosphatase PTP1C associates with Vav, Grb2, and mSos1 in hematopoietic cells. J Biol Chem. 1996;271:3856-62 pubmed
- Gout I, Dhand R, Hiles I, Fry M, Panayotou G, Das P, et al. The GTPase dynamin binds to and is activated by a subset of SH3 domains. Cell. 1993;75:25-36 pubmed
- Cheng A, Saxton T, Sakai R, Kulkarni S, Mbamalu G, Vogel W, et al. Mammalian Grb2 regulates multiple steps in embryonic development and malignant transformation. Cell. 1998;95:793-803 pubmed..Grb2 acts physiologically as an adaptor, since replacing the C terminus of the Ras activator Sos1 with the Grb2 SH2 domain yields a fusion protein that largely rescues the defects caused by the Grb2 mutation...
- Gaikwad J, Cavender A, D Souza R. Identification of tooth-specific downstream targets of Runx2. Gene. 2001;279:91-7 pubmed..In conclusion, we have successfully generated a library enriched in genes expressed in Runx2(+/+) molar tooth organs and performed preliminary studies to assess the role of Zfp in tooth development. ..
- Fishel R, Lescoe M, Rao M, Copeland N, Jenkins N, Garber J, et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993;75:1027-38 pubmed..These data and reports indicating that S. cerevisiae msh2 mutations cause an instability of dinucleotide repeats like those associated with HNPCC suggest that hMSH2 is the HNPCC gene. ..
- Mathew P, Morris S, Kane J, Shurtleff S, Pasquini M, Jenkins N, et al. Localization of the murine homolog of the anaplastic lymphoma kinase (AlK) gene on mouse chromosome 17. Cytogenet Cell Genet. 1995;70:143-4 pubmed..This assignment further confirms the homology between a portion of the distal Chromosome 17 and the short arm of human chromosome 2 and extends this region in the mouse by an additional 3 cM. ..