Gene Symbol: Lsc
Description: Rho guanine nucleotide exchange factor (GEF) 1
Alias: Lbcl2, Lsc, rho guanine nucleotide exchange factor 1, lbc's second cousin, lymphoid blast crisis-like 2
Species: mouse
Products:     Lsc

Top Publications

  1. Harenberg A, Girkontaite I, Giehl K, Fischer K. The Lsc RhoGEF mediates signaling from thromboxane A2 to actin polymerization and apoptosis in thymocytes. Eur J Immunol. 2005;35:1977-86 pubmed
    The Lsc RhoGEF (also known as p115-RhoGEF) is a GTP exchange factor (GEF), an activator of GTPases of the Rho family...
  2. Girkontaite I, Missy K, Sakk V, Harenberg A, Tedford K, Pötzel T, et al. Lsc is required for marginal zone B cells, regulation of lymphocyte motility and immune responses. Nat Immunol. 2001;2:855-62 pubmed
    b>Lsc (the murine homolog of human p115 Rho GEF) is a member of the Dbl-homology family of GTP exchange factors and is a specific activator of Rho...
  3. Francis S, Shen X, Young J, Kaul P, Lerner D. Rho GEF Lsc is required for normal polarization, migration, and adhesion of formyl-peptide-stimulated neutrophils. Blood. 2006;107:1627-35 pubmed
    ..b>Lsc is a RhoA guanine nucleotide exchange factor that binds the heterotrimeric G-protein alpha-subunits, Galpha12 and ..
  4. Rubtsov A, Strauch P, Digiacomo A, Hu J, Pelanda R, Torres R. Lsc regulates marginal-zone B cell migration and adhesion and is required for the IgM T-dependent antibody response. Immunity. 2005;23:527-38 pubmed
    ..Here, we demonstrate that Lsc, a protein that regulates G protein-coupled-receptor signaling and RhoA activation, is required by B lymphocytes ..
  5. Glaven J, Whitehead I, Nomanbhoy T, Kay R, Cerione R. Lfc and Lsc oncoproteins represent two new guanine nucleotide exchange factors for the Rho GTP-binding protein. J Biol Chem. 1996;271:27374-81 pubmed
    Lfc and Lsc are two recently identified oncoproteins that contain a Dbl homology domain in tandem with a pleckstrin homology domain and thus share sequence similarity with a number of other growth regulatory proteins including Dbl, Tiam-..
  6. Ma X, Zhao Y, Daaka Y, Nie Z. Acute activation of ?2-adrenergic receptor regulates focal adhesions through ?Arrestin2- and p115RhoGEF protein-mediated activation of RhoA. J Biol Chem. 2012;287:18925-36 pubmed publisher
    ..These results suggest that ?Arrestin2 may serve as a convergence point for non-G(12/13) and non-G(q) protein-coupled receptors to activate RhoA...
  7. Hartney J, Gustafson C, Bowler R, Pelanda R, Torres R. Thromboxane receptor signaling is required for fibronectin-induced matrix metalloproteinase 9 production by human and murine macrophages and is attenuated by the Arhgef1 molecule. J Biol Chem. 2011;286:44521-31 pubmed publisher
    ..Finally, we show that the expression of ARHGEF1 by human peripheral blood monocytes varies between individuals and inversely correlates with fibronectin-mediated MMP9 production. ..
  8. Zizer E, Beilke S, Bauerle T, Schilling K, Möhnle U, Adler G, et al. Loss of Lsc/p115 protein leads to neuronal hypoplasia in the esophagus and an achalasia-like phenotype in mice. Gastroenterology. 2010;139:1344-54 pubmed publisher
    b>Lsc/p115 originally was described as hematopoietic Ras homologous protein guanine exchange factor (Rho-GEF) regulating leukocyte migration, adhesion, and marginal zone B-cell homeostasis...
  9. Guilluy C, Bregeon J, Toumaniantz G, Rolli Derkinderen M, Retailleau K, Loufrani L, et al. The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure. Nat Med. 2010;16:183-90 pubmed publisher
    ..Our results show that control of RhoA signaling through Arhgef1 is central to the development of angiotensin II-dependent hypertension and identify Arhgef1 as a potential target for the treatment of hypertension. ..

More Information


  1. Chen Z, Singer W, Danesh S, Sternweis P, Sprang S. Recognition of the activated states of Galpha13 by the rgRGS domain of PDZRhoGEF. Structure. 2008;16:1532-43 pubmed publisher
    ..Replacement of key residues in this motif with their counterparts in p115RhoGEF confers GAP activity. ..
  2. Rubtsov A, Swanson C, Troy S, Strauch P, Pelanda R, Torres R. TLR agonists promote marginal zone B cell activation and facilitate T-dependent IgM responses. J Immunol. 2008;180:3882-8 pubmed
    ..Together, these data demonstrate that in vivo TLR agonist treatment enhances the early production of Ag-specific IgM and activates MZ B cells to promote their relocation. ..
  3. Xiang X, Li S, Zhuang X, Shi L. Arhgef1 negatively regulates neurite outgrowth through activation of RhoA signaling pathways. FEBS Lett. 2016;590:2940-55 pubmed publisher
    ..Collectively, these findings reveal that Arhgef1 functions as a negative regulator of neurite outgrowth through regulating RhoA-cofilin pathway and actin dynamics. ..
  4. Green J, Suzuki K, Cho B, Willison L, Palmer D, Allen C, et al. The sphingosine 1-phosphate receptor S1P? maintains the homeostasis of germinal center B cells and promotes niche confinement. Nat Immunol. 2011;12:672-80 pubmed publisher
    ..We suggest that by inhibiting Akt activation and migration, S1P(2) helps restrict GC B cell survival and localization to an S1P-low niche at the follicle center. ..
  5. Peng J, He F, Zhang C, Deng X, Yin F. Protein kinase C-? signals P115RhoGEF phosphorylation and RhoA activation in TNF-?-induced mouse brain microvascular endothelial cell barrier dysfunction. J Neuroinflammation. 2011;8:28 pubmed publisher
    ..Taken together, our results show that PKC-? phosphorylation of p115RhoGEF mediates TNF-? signaling to RhoA, and that this plays a critical role in signaling F-actin rearrangement and barrier dysfunction in BMECs. ..
  6. Whitehead I, Khosravi Far R, Kirk H, Trigo Gonzalez G, Der C, Kay R. Expression cloning of lsc, a novel oncogene with structural similarities to the Dbl family of guanine nucleotide exchange factors. J Biol Chem. 1996;271:18643-50 pubmed
    ..The transforming cDNA encodes a truncated protein (designated Lsc) with a region of sequence similarity to the product of the lbc oncogene...
  7. Hu J, Strauch P, Rubtsov A, Donovan E, Pelanda R, Torres R. Lsc activity is controlled by oligomerization and regulates integrin adhesion. Mol Immunol. 2008;45:1825-36 pubmed
    b>Lsc is a hematopoietic-restricted protein that functions as an effector of G alpha(12/13)-associated G-protein coupled receptors that activates RhoA...
  8. Chattopadhyay G, Khan A, Sen G, Colino J, DuBois W, Rubtsov A, et al. Transgenic expression of Bcl-xL or Bcl-2 by murine B cells enhances the in vivo antipolysaccharide, but not antiprotein, response to intact Streptococcus pneumoniae. J Immunol. 2007;179:7523-34 pubmed
    ..This was associated with increased clonal expansion and decreased apoptosis. Using Lsc(-/-) mice, the Pn-induced IgG response specific for the capsular PS was found to be almost entirely dependent on ..
  9. Brown J, Taube C, Miyahara N, Koya T, Pelanda R, Gelfand E, et al. Arhgef1 is required by T cells for the development of airway hyperreactivity and inflammation. Am J Respir Crit Care Med. 2007;176:10-9 pubmed
    ..Moreover, a deficiency in Arhgef1 results in reduced T cell-CD11c+ antigen-presenting cell interaction, and likely underscores the inability of Arhgef1-/- mice to mount an adaptive immune response to airway challenge. ..
  10. Kostenko E, Olabisi O, Sahay S, Rodriguez P, Whitehead I. Ccpg1, a novel scaffold protein that regulates the activity of the Rho guanine nucleotide exchange factor Dbs. Mol Cell Biol. 2006;26:8964-75 pubmed
  11. Eisenhaure T, Francis S, Willison L, Coughlin S, Lerner D. The Rho guanine nucleotide exchange factor Lsc homo-oligomerizes and is negatively regulated through domains in its carboxyl terminus that are absent in novel splenic isoforms. J Biol Chem. 2003;278:30975-84 pubmed
    ..b>Lsc/p115-RhoGEF is a Rho-specific GEF required for normal B and T lymphocyte function...
  12. Martina J, Moriyama K, Bonifacino J. BLOC-3, a protein complex containing the Hermansky-Pudlak syndrome gene products HPS1 and HPS4. J Biol Chem. 2003;278:29376-84 pubmed
  13. Colino J, Chattopadhyay G, Sen G, Chen Q, Lees A, Canaday D, et al. Parameters underlying distinct T cell-dependent polysaccharide-specific IgG responses to an intact gram-positive bacterium versus a soluble conjugate vaccine. J Immunol. 2009;183:1551-9 pubmed publisher
  14. Hartney J, Brown J, Chu H, Chang L, Pelanda R, Torres R. Arhgef1 regulates alpha5beta1 integrin-mediated matrix metalloproteinase expression and is required for homeostatic lung immunity. Am J Pathol. 2010;176:1157-68 pubmed publisher
    ..Together these data demonstrate that Arhgef1 regulates alpha5beta1-mediated MMP expression by macrophages and that loss of Arhgef1 by leukocytes leads to pulmonary pathology. ..
  15. Muppidi J, Schmitz R, Green J, Xiao W, Larsen A, Braun S, et al. Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma. Nature. 2014;516:254-8 pubmed publisher
    ..These findings identify a Gα13-dependent pathway that exerts dual actions in suppressing growth and blocking dissemination of germinal centre B cells that is frequently disrupted in germinal centre B-cell-derived lymphoma. ..
  16. Aasheim H, Pedeutour F, Smeland E. Characterization, expression and chromosomal localization of a human gene homologous to the mouse Lsc oncogene, with strongest expression in hematopoetic tissues. Oncogene. 1997;14:1747-52 pubmed
    ..Recently, however, a mouse cDNA (Lsc) with high homology to sub1.5 was identified, indicating that the sub1...
  17. Xiang X, Zhuang X, Li S, Shi L. Arhgef1 is expressed in cortical neural progenitor cells and regulates neurite outgrowth of newly differentiated neurons. Neurosci Lett. 2017;638:27-34 pubmed publisher
    ..These findings reveal that Arhgef1 controls the process of neurite formation in newborn cortical neurons derived from NPCs. ..