Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

PNAS 101 (20): 7618-7623

Copyright © 2004 by the National Academy of Sciences.


Cell Biology

Rational design and characterization of a Rac GTPase-specific small molecule inhibitor

Yuan Gao *, J. Bradley Dickerson {dagger}, Fukun Guo *, Jie Zheng {dagger}, and Yi Zheng *, {ddagger}

*Division of Experimental Hematology, Children's Hospital Research Foundation, Cincinnati, OH 45229; and {dagger}Department of Structure Biology, St. Jude Children's Research Hospital, Memphis, TN 38105

Edited by Lewis C. Cantley, Harvard Institutes of Medicine, Boston, MA

Accepted for publication March 30, 2004.

Received for publication November 13, 2003.

Abstract: The signaling pathways mediated by Rho family GTPases have been implicated in many aspects of cell biology. The specificity of the pathways is achieved in part by the selective interaction between Dbl family guanine nucleotide exchange factors (GEFs) and their Rho GTPase substrates. Here, we report a first-generation small-molecule inhibitor of Rac GTPase targeting Rac activation by GEF. The chemical compound NSC23766was identified by a structure-based virtual screening of compounds that fit into a surface groove of Rac1 known to be critical for GEF specification. In vitro it could effectively inhibit Rac1 binding and activation by the Rac-specific GEF Trio or Tiam1 in a dose-dependent manner without interfering with the closely related Cdc42 or RhoA binding or activation by their respective GEFs or with Rac1 interaction with BcrGAP or effector PAK1. In cells, it potently blocked serum or platelet-derived growth factor-induced Rac1 activation and lamellipodia formation without affecting the activity of endogenous Cdc42 or RhoA. Moreover, this compound reduced Trio or Tiam1 but not Vav, Lbc, Intersectin, or a constitutively active Rac1 mutant-stimulated cell growth and suppressed Trio, Tiam1, or Ras-induced cell transformation. When applied to human prostate cancer PC-3 cells, it was able to inhibit the proliferation, anchorage-independent growth and invasion phenotypes that require the endogenous Rac1 activity. Thus, NSC23766constitutes a Rac-specific small-molecule inhibitor that could be useful to study the role of Rac in various cellular functions and to reverse tumor cell phenotypes associated with Rac deregulation.


This paper was submitted directly (Track II) to the PNAS office.

Abbreviations: GEF, guanine nucleotide exchange factor; PDGF, platelet-derived growth factor.

{ddagger} To whom correspondence should be addressed at: Division of Experimental Hematology, Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229. E-mail: yi.zheng{at}chmcc.org.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Wnt5a-Rac1-NF-{kappa}B Homeostatic Circuitry Sustains Innate Immune Functions in Macrophages.
D. Naskar, G. Maiti, A. Chakraborty, A. Roy, D. Chattopadhyay, and M. Sen (2014)
J. Immunol. 192, 4386-4397
   Abstract »    Full Text »    PDF »
Caveolin-1 Mediates Salmonella Invasion via the Regulation of SopE-dependent Rac1 Activation and Actin Reorganization.
J. S. Lim, M. Shin, H.-J. Kim, K. S. Kim, H. E. Choy, and K. A. Cho (2014)
The Journal of Infectious Disease
   Abstract »    Full Text »    PDF »
Rho GTPases Control Ciliary Epithelium Cells Proliferation and Progenitor Profile Induction In Vivo.
C. B. Del Debbio, M. F. Santos, C. Y. I. Yan, I. Ahmad, and D. E. Hamassaki (2014)
Invest. Ophthalmol. Vis. Sci. 55, 2631-2641
   Abstract »    Full Text »    PDF »
A combination of Wnt and growth factor signaling induces Arl4c expression to form epithelial tubular structures.
S. Matsumoto, S. Fujii, A. Sato, S. Ibuka, Y. Kagawa, M. Ishii, and A. Kikuchi (2014)
EMBO J. 33, 702-718
   Abstract »    Full Text »    PDF »
The small GTPase Rac1 is required for smooth muscle contraction.
A. Rahman, B. Davis, C. Lovdahl, V. T. Hanumaiah, R. Feil, C. Brakebusch, and A. Arner (2014)
J. Physiol. 592, 915-926
   Abstract »    Full Text »    PDF »
Stimulation of G Protein-Coupled Bile Acid Receptor Enhances Vascular Endothelial Barrier Function via Activation of Protein Kinase A and Rac1.
T. Kida, K. Omori, M. Hori, H. Ozaki, and T. Murata (2014)
J. Pharmacol. Exp. Ther. 348, 125-130
   Abstract »    Full Text »    PDF »
Activation of Rac by Asef2 promotes myosin II-dependent contractility to inhibit cell migration on type I collagen.
L. Jean, D. Majumdar, M. Shi, L. E. Hinkle, N. L. Diggins, M. Ao, J. A. Broussard, J. C. Evans, D. P. Choma, and D. J. Webb (2013)
J. Cell Sci. 126, 5585-5597
   Abstract »    Full Text »    PDF »
The Rac-GAP Bcr is a novel regulator of the Par complex that controls cell polarity.
A. S. Narayanan, S. B. Reyes, K. Um, J. H. McCarty, and K. F. Tolias (2013)
Mol. Biol. Cell 24, 3857-3868
   Abstract »    Full Text »    PDF »
A functional siRNA screen identifies genes modulating angiotensin II-mediated EGFR transactivation.
A. J. George, B. W. Purdue, C. M. Gould, D. W. Thomas, Y. Handoko, H. Qian, G. A. Quaife-Ryan, K. A. Morgan, K. J. Simpson, W. G. Thomas, et al. (2013)
J. Cell Sci. 126, 5377-5390
   Abstract »    Full Text »    PDF »
A synthetic nanofibrillar matrix promotes in vitro hepatic differentiation of embryonic stem cells and induced pluripotent stem cells.
T. Yamazoe, N. Shiraki, M. Toyoda, N. Kiyokawa, H. Okita, Y. Miyagawa, H. Akutsu, A. Umezawa, Y. Sasaki, K. Kume, et al. (2013)
J. Cell Sci. 126, 5391-5399
   Abstract »    Full Text »    PDF »
Phosphorylation of Rac1 T108 by Extracellular Signal-Regulated Kinase in Response to Epidermal Growth Factor: a Novel Mechanism To Regulate Rac1 Function.
J. Tong, L. Li, B. Ballermann, and Z. Wang (2013)
Mol. Cell. Biol. 33, 4538-4551
   Abstract »    Full Text »    PDF »
A Specific PTPRC/CD45 Phosphorylation Event Governed by Stem Cell Chemokine CXCL12 Regulates Primitive Hematopoietic Cell Motility.
A. J. K. Williamson, A. Pierce, E. Jaworska, C. Zhou, M. Aspinall-O'Dea, L. Lancashire, R. D. Unwin, S. A. Abraham, M. J. Walker, S. Cadecco, et al. (2013)
Mol. Cell. Proteomics 12, 3319-3329
   Abstract »    Full Text »    PDF »
How T cells trigger the dissociation of the endothelial receptor phosphatase VE-PTP from VE-cadherin.
M. Vockel and D. Vestweber (2013)
Blood 122, 2512-2522
   Abstract »    Full Text »    PDF »
NSC23766, a Widely Used Inhibitor of Rac1 Activation, Additionally Acts as a Competitive Antagonist at Muscarinic Acetylcholine Receptors.
M. Levay, K. A. Krobert, K. Wittig, N. Voigt, M. Bermudez, G. Wolber, D. Dobrev, F. O. Levy, and T. Wieland (2013)
J. Pharmacol. Exp. Ther. 347, 69-79
   Abstract »    Full Text »    PDF »
RAC1: An Emerging Therapeutic Option for Targeting Cancer Angiogenesis and Metastasis.
H. K. Bid, R. D. Roberts, P. K. Manchanda, and P. J. Houghton (2013)
Mol. Cancer Ther. 12, 1925-1934
   Abstract »    Full Text »    PDF »
Roles of Rho GTPases in leucocyte and leukaemia cell transendothelial migration.
E. Infante and A. J. Ridley (2013)
Phil Trans R Soc B 368, 20130013
   Abstract »    Full Text »    PDF »
FMNL1 promotes proliferation and migration of leukemia cells.
P. Favaro, F. Traina, J. A. Machado-Neto, M. Lazarini, M. R. Lopes, J. K. N. Pereira, F. F. Costa, E. Infante, A. J. Ridley, and S. T. O. Saad (2013)
J. Leukoc. Biol. 94, 503-512
   Abstract »    Full Text »    PDF »
Combined Inhibition of HER1/EGFR and RAC1 Results in a Synergistic Antiproliferative Effect on Established and Primary Cultured Human Glioblastoma Cells.
G. Karpel-Massler, M.- A. Westhoff, S. Zhou, L. Nonnenmacher, A. Dwucet, R. E. Kast, M. G. Bachem, C. R. Wirtz, K.-M. Debatin, and M.-E. Halatsch (2013)
Mol. Cancer Ther. 12, 1783-1795
   Abstract »    Full Text »    PDF »
Tumor Cell Migration and Invasion Are Enhanced by Depletion of Rap1 GTPase-activating Protein (Rap1GAP).
O. M. Tsygankova, H. Wang, and J. L. Meinkoth (2013)
J. Biol. Chem. 288, 24636-24646
   Abstract »    Full Text »    PDF »
Single Quantum Dot Tracking Reveals that an Individual Multivalent HIV-1 Tat Protein Transduction Domain Can Activate Machinery for Lateral Transport and Endocytosis.
Y. Suzuki, C. N. Roy, W. Promjunyakul, H. Hatakeyama, K. Gonda, J. Imamura, B. Vasudevanpillai, N. Ohuchi, M. Kanzaki, H. Higuchi, et al. (2013)
Mol. Cell. Biol. 33, 3036-3049
   Abstract »    Full Text »    PDF »
Scavengers of reactive oxygen species, paracalcitol, RhoA, and Rac-1 inhibitors and tacrolimus inhibit angiotensin II-induced actions on glomerular permeability.
J. Axelsson, A. Rippe, K. Sverrisson, and B. Rippe (2013)
Am J Physiol Renal Physiol 305, F237-F243
   Abstract »    Full Text »    PDF »
STAT3 mediates oncogenic addiction to TEL-AML1 in t(12;21) acute lymphoblastic leukemia.
M. Mangolini, J. de Boer, V. Walf-Vorderwulbecke, R. Pieters, M. L. den Boer, and O. Williams (2013)
Blood 122, 542-549
   Abstract »    Full Text »    PDF »
The Atypical Guanine Nucleotide Exchange Factor Dock4 Regulates Neurite Differentiation through Modulation of Rac1 GTPase and Actin Dynamics.
Y. Xiao, Y. Peng, J. Wan, G. Tang, Y. Chen, J. Tang, W.-C. Ye, N. Y. Ip, and L. Shi (2013)
J. Biol. Chem. 288, 20034-20045
   Abstract »    Full Text »    PDF »
The Rho-GEF Trio regulates a novel pro-inflammatory pathway through the transcription factor Ets2.
J. Van Rijssel, I. Timmerman, F. P. J. Van Alphen, M. Hoogenboezem, O. Korchynskyi, D. Geerts, J. Geissler, K. A. Reedquist, H. W. M. Niessen, and J. D. Van Buul (2013)
Biology Open 2, 569-579
   Abstract »    Full Text »    PDF »
Activation of the small G-protein Rac by human rhinovirus attenuates the TLR3/IFN-{alpha} axis while promoting CCL2 release in human monocyte-lineage cells.
M. T. Schreiber, B. Schuler, L. Li, and D. J. Hall (2013)
Innate Immunity 19, 278-289
   Abstract »    Full Text »    PDF »
CIP4 coordinates with phospholipids and actin-associated proteins to localize to the protruding edge and produce actin ribs and veils.
W. Saengsawang, K. L. Taylor, D. C. Lumbard, K. Mitok, A. Price, L. Pietila, T. M. Gomez, and E. W. Dent (2013)
J. Cell Sci. 126, 2411-2423
   Abstract »    Full Text »    PDF »
Characterization of a Cdc42 Protein Inhibitor and Its Use as a Molecular Probe.
L. Hong, S. R. Kenney, G. K. Phillips, D. Simpson, C. E. Schroeder, J. Noth, E. Romero, S. Swanson, A. Waller, J. J. Strouse, et al. (2013)
J. Biol. Chem. 288, 8531-8543
   Abstract »    Full Text »    PDF »
Prostaglandin D2-DP Signaling Promotes Endothelial Barrier Function via the cAMP/PKA/Tiam1/Rac1 Pathway.
K. Kobayashi, Y. Tsubosaka, M. Hori, S. Narumiya, H. Ozaki, and T. Murata (2013)
Arterioscler Thromb Vasc Biol 33, 565-571
   Abstract »    Full Text »    PDF »
The Planar Cell Polarity Pathway Drives Pathogenesis of Chronic Lymphocytic Leukemia by the Regulation of B-Lymphocyte Migration.
M. Kaucka, K. Plevova, S. Pavlova, P. Janovska, A. Mishra, J. Verner, J. Prochazkova, P. Krejci, J. Kotaskova, P. Ovesna, et al. (2013)
Cancer Res. 73, 1491-1501
   Abstract »    Full Text »    PDF »
Small-molecule inhibitors targeting G-protein-coupled Rho guanine nucleotide exchange factors.
X. Shang, F. Marchioni, C. R. Evelyn, N. Sipes, X. Zhou, W. Seibel, M. Wortman, and Y. Zheng (2013)
PNAS 110, 3155-3160
   Abstract »    Full Text »    PDF »
Small molecule targeting Cdc42-intersectin interaction disrupts Golgi organization and suppresses cell motility.
A. Friesland, Y. Zhao, Y.-H. Chen, L. Wang, H. Zhou, and Q. Lu (2013)
PNAS 110, 1261-1266
   Abstract »    Full Text »    PDF »
Calcineurin-dependent cofilin activation and increased retrograde actin flow drive 5-HT-dependent neurite outgrowth in Aplysia bag cell neurons.
X.-F. Zhang, C. Hyland, D. Van Goor, and P. Forscher (2012)
Mol. Biol. Cell 23, 4833-4848
   Abstract »    Full Text »    PDF »
Frat2 mediates the oncogenic activation of Rac by MLL fusions.
V. Walf-Vorderwulbecke, J. de Boer, S. J. Horton, R. van Amerongen, N. Proost, A. Berns, and O. Williams (2012)
Blood 120, 4819-4828
   Abstract »    Full Text »    PDF »
Rac1 Controls Schwann Cell Myelination through cAMP and NF2/merlin.
L. Guo, C. Moon, K. Niehaus, Y. Zheng, and N. Ratner (2012)
J. Neurosci. 32, 17251-17261
   Abstract »    Full Text »    PDF »
Rac1 Protein Signaling Is Required for DNA Damage Response Stimulated by Topoisomerase II Poisons.
S. C. Huelsenbeck, A. Schorr, W. P. Roos, J. Huelsenbeck, C. Henninger, B. Kaina, and G. Fritz (2012)
J. Biol. Chem. 287, 38590-38599
   Abstract »    Full Text »    PDF »
Myopodin isoforms alter the chemokinetic response of PC3 cells in response to different migration stimuli via differential effects on Rho-ROCK signaling pathways.
F. Kai, K. Tanner, C. King, and R. Duncan (2012)
Carcinogenesis 33, 2100-2107
   Abstract »    Full Text »    PDF »
Actopaxin ({alpha}-Parvin) Phosphorylation Is Required for Matrix Degradation and Cancer Cell Invasion.
J. Pignatelli, S. E. LaLonde, D. P. LaLonde, D. Clarke, and C. E. Turner (2012)
J. Biol. Chem. 287, 37309-37320
   Abstract »    Full Text »    PDF »
TIPE2 Controls Innate Immunity to RNA by Targeting the Phosphatidylinositol 3-Kinase-Rac Pathway.
H. Sun, G. Zhuang, L. Chai, Z. Wang, D. Johnson, Y. Ma, and Y. H. Chen (2012)
J. Immunol. 189, 2768-2773
   Abstract »    Full Text »    PDF »
Oxidized LDL/CD36 interaction induces loss of cell polarity and inhibits macrophage locomotion.
Y. M. Park, J. A. Drazba, A. Vasanji, T. Egelhoff, M. Febbraio, and R. L. Silverstein (2012)
Mol. Biol. Cell 23, 3057-3068
   Abstract »    Full Text »    PDF »
The Rho-guanine nucleotide exchange factor Trio controls leukocyte transendothelial migration by promoting docking structure formation.
J. van Rijssel, J. Kroon, M. Hoogenboezem, F. P. J. van Alphen, R. J. de Jong, E. Kostadinova, D. Geerts, P. L. Hordijk, and J. D. van Buul (2012)
Mol. Biol. Cell 23, 2831-2844
   Abstract »    Full Text »    PDF »
Cadherin point mutations alter cell sorting and modulate GTPase signaling.
H. Tabdili, A. K. Barry, M. D. Langer, Y.-H. Chien, Q. Shi, K. J. Lee, S. Lu, and D. E. Leckband (2012)
J. Cell Sci. 125, 3299-3309
   Abstract »    Full Text »    PDF »
Rac1 Inhibition Prevents Tissue Contraction and MMP Mediated Matrix Remodeling in the Conjunctiva.
V. E. Tovell, C. Y. Chau, P. T. Khaw, and M. Bailly (2012)
Invest. Ophthalmol. Vis. Sci. 53, 4682-4691
   Abstract »    Full Text »    PDF »
Signaling and cytoskeletal requirements in erythroblast enucleation.
D. G. Konstantinidis, S. Pushkaran, J. F. Johnson, J. A. Cancelas, S. Manganaris, C. E. Harris, D. A. Williams, Y. Zheng, and T. A. Kalfa (2012)
Blood 119, 6118-6127
   Abstract »    Full Text »    PDF »
Vav3-Rac1 Signaling Regulates Prostate Cancer Metastasis with Elevated Vav3 Expression Correlating with Prostate Cancer Progression and Posttreatment Recurrence.
K.-T. Lin, J. Gong, C.-F. Li, T.-H. Jang, W.-L. Chen, H.-J. Chen, and L.-H. Wang (2012)
Cancer Res. 72, 3000-3009
   Abstract »    Full Text »    PDF »
Maladaptive Dendritic Spine Remodeling Contributes to Diabetic Neuropathic Pain.
A. M. Tan, O. A. Samad, T. Z. Fischer, P. Zhao, A.-K. Persson, and S. G. Waxman (2012)
J. Neurosci. 32, 6795-6807
   Abstract »    Full Text »    PDF »
Rac2-MRC-cIII-generated ROS cause genomic instability in chronic myeloid leukemia stem cells and primitive progenitors.
M. Nieborowska-Skorska, P. K. Kopinski, R. Ray, G. Hoser, D. Ngaba, S. Flis, K. Cramer, M. M. Reddy, M. Koptyra, T. Penserga, et al. (2012)
Blood 119, 4253-4263
   Abstract »    Full Text »    PDF »
Characterization of EHop-016, Novel Small Molecule Inhibitor of Rac GTPase.
B. L. Montalvo-Ortiz, L. Castillo-Pichardo, E. Hernandez, T. Humphries-Bickley, A. De La Mota-Peynado, L. A. Cubano, C. P. Vlaar, and S. Dharmawardhane (2012)
J. Biol. Chem. 287, 13228-13238
   Abstract »    Full Text »    PDF »
Rac1 Protein Regulates Glycogen Phosphorylase Activation and Controls Interleukin (IL)-2-dependent T Cell Proliferation.
O. Arrizabalaga, H. M. Lacerda, A. M. Zubiaga, and J. L. Zugaza (2012)
J. Biol. Chem. 287, 11878-11890
   Abstract »    Full Text »    PDF »
Role for the Guanine Nucleotide Exchange Factor Phosphatidylinositol-3,4,5-Trisphosphate-Dependent Rac Exchanger 1 in Platelet Secretion and Aggregation.
F. Qian, G. C. Le Breton, J. Chen, J. Deng, J. W. Christman, D. Wu, and R. D. Ye (2012)
Arterioscler Thromb Vasc Biol 32, 768-777
   Abstract »    Full Text »    PDF »
Regulation of CXCR4 conformation by the small GTPase Rac1: implications for HIV infection.
Y. Zoughlami, C. Voermans, K. Brussen, K. A. van Dort, N. A. Kootstra, D. Maussang, M. J. Smit, P. L. Hordijk, and P. B. van Hennik (2012)
Blood 119, 2024-2032
   Abstract »    Full Text »    PDF »
Interplay between {beta}1-Integrin and Rho Signaling Regulates Differential Scattering and Motility of Pancreatic Cancer Cells by Snail and Slug Proteins.
M. A. Shields, S. B. Krantz, D. J. Bentrem, S. Dangi-Garimella, and H. G. Munshi (2012)
J. Biol. Chem. 287, 6218-6229
   Abstract »    Full Text »    PDF »
NADPH oxidase-mediated Rac1 GTP activity is necessary for nongenomic actions of the mineralocorticoid receptor in the CA1 region of the rat hippocampus.
F. Kawakami-Mori, T. Shimosawa, S. Mu, H. Wang, S. Ogura, Y. Yatomi, and T. Fujita (2012)
Am J Physiol Endocrinol Metab 302, E425-E432
   Abstract »    Full Text »    PDF »
Bone Morphogenetic Protein 4 Promotes Vascular Smooth Muscle Contractility by Activating MicroRNA-21 (miR-21), which Down-regulates Expression of Family of Dedicator of Cytokinesis (DOCK) Proteins.
H. Kang, B. N. Davis-Dusenbery, P. H. Nguyen, A. Lal, J. Lieberman, L. Van Aelst, G. Lagna, and A. Hata (2012)
J. Biol. Chem. 287, 3976-3986
   Abstract »    Full Text »    PDF »
Small Rho GTPases and Cholesterol Biosynthetic Pathway Intermediates in African Swine Fever Virus Infection.
J. I. Quetglas, B. Hernaez, I. Galindo, R. Munoz-Moreno, M. A. Cuesta-Geijo, and C. Alonso (2012)
J. Virol. 86, 1758-1767
   Abstract »    Full Text »    PDF »
Rap1-Rac1 Circuits Potentiate Platelet Activation.
L. Stefanini, Y. Boulaftali, T. D. Ouellette, M. Holinstat, L. Desire, B. Leblond, P. Andre, P. B. Conley, and W. Bergmeier (2012)
Arterioscler Thromb Vasc Biol 32, 434-441
   Abstract »    Full Text »    PDF »
Role of Rho GTPases in Human Trophoblast Migration Induced by IGFBP1.
J. Saso, S.-K. Shields, Y. Zuo, and C. Chakraborty (2012)
Biol Reprod 86, 1-9
   Abstract »    Full Text »    PDF »
Enucleation of human erythroblasts involves non-muscle myosin IIB.
K. Ubukawa, Y.-M. Guo, M. Takahashi, M. Hirokawa, Y. Michishita, M. Nara, H. Tagawa, N. Takahashi, A. Komatsuda, W. Nunomura, et al. (2012)
Blood 119, 1036-1044
   Abstract »    Full Text »    PDF »
Novel Mechanistic Link between Focal Adhesion Remodeling and Glucose-stimulated Insulin Secretion.
D. Rondas, A. Tomas, M. Soto-Ribeiro, B. Wehrle-Haller, and P. A. Halban (2012)
J. Biol. Chem. 287, 2423-2436
   Abstract »    Full Text »    PDF »
Involvement of 14-3-3 Proteins in the Second Epidermal Growth Factor-induced Wave of Rac1 Activation in the Process of Cell Migration.
H. Kobayashi, Y. Ogura, M. Sawada, R. Nakayama, K. Takano, Y. Minato, Y. Takemoto, E. Tashiro, H. Watanabe, and M. Imoto (2011)
J. Biol. Chem. 286, 39259-39268
   Abstract »    Full Text »    PDF »
Angiopoietin-1 Requires IQ Domain GTPase-Activating Protein 1 to Activate Rac1 and Promote Endothelial Barrier Defense.
S. David, C. C. Ghosh, A. Mukherjee, and S. M. Parikh (2011)
Arterioscler Thromb Vasc Biol 31, 2643-2652
   Abstract »    Full Text »    PDF »
A-kinase anchoring proteins: scaffolding proteins in the heart.
D. Diviani, K. L. Dodge-Kafka, J. Li, and M. S. Kapiloff (2011)
Am J Physiol Heart Circ Physiol 301, H1742-H1753
   Abstract »    Full Text »    PDF »
Inducible nitric oxide synthase-nitric oxide signaling mediates the mitogenic activity of Rac1 during endochondral bone growth.
G. Wang, Q. Yan, A. Woods, L. A. Aubrey, Q. Feng, and F. Beier (2011)
J. Cell Sci. 124, 3405-3413
   Abstract »    Full Text »    PDF »
Stereotyped fetal brain disorganization is induced by hypoxia and requires lysophosphatidic acid receptor 1 (LPA1) signaling.
K. J. Herr, D. R. Herr, C.-W. Lee, K. Noguchi, and J. Chun (2011)
PNAS 108, 15444-15449
   Abstract »    Full Text »    PDF »
The Universally Conserved Prokaryotic GTPases.
N. Verstraeten, M. Fauvart, W. Versees, and J. Michiels (2011)
Microbiol. Mol. Biol. Rev. 75, 507-542
   Abstract »    Full Text »    PDF »
HOXC8-Dependent Cadherin 11 Expression Facilitates Breast Cancer Cell Migration through Trio and Rac.
Y. Li, Z. Guo, H. Chen, Z. Dong, Z. K. Pan, H. Ding, S.-B. Su, and S. Huang (2011)
Genes & Cancer 2, 880-888
   Abstract »    Full Text »    PDF »
Essential Role for Vav Guanine Nucleotide Exchange Factors in Brain-Derived Neurotrophic Factor-Induced Dendritic Spine Growth and Synapse Plasticity.
C. F. Hale, K. C. Dietz, J. A. Varela, C. B. Wood, B. C. Zirlin, L. S. Leverich, R. W. Greene, and C. W. Cowan (2011)
J. Neurosci. 31, 12426-12436
   Abstract »    Full Text »    PDF »
WAVE regulatory complex activation by cooperating GTPases Arf and Rac1.
V. Koronakis, P. J. Hume, D. Humphreys, T. Liu, O. Horning, O. N. Jensen, and E. J. McGhie (2011)
PNAS 108, 14449-14454
   Abstract »    Full Text »    PDF »
Kif3a regulates planar polarization of auditory hair cells through both ciliary and non-ciliary mechanisms.
C. W. Sipe and X. Lu (2011)
Development 138, 3441-3449
   Abstract »    Full Text »    PDF »
One Percent Tenofovir Applied Topically to Humanized BLT Mice and Used According to the CAPRISA 004 Experimental Design Demonstrates Partial Protection from Vaginal HIV Infection, Validating the BLT Model for Evaluation of New Microbicide Candidates.
P. W. Denton, F. Othieno, F. Martinez-Torres, W. Zou, J. F. Krisko, E. Fleming, S. Zein, D. A. Powell, A. Wahl, Y. T. Kwak, et al. (2011)
J. Virol. 85, 7582-7593
   Abstract »    Full Text »    PDF »
Rhinovirus-Induced Barrier Dysfunction in Polarized Airway Epithelial Cells Is Mediated by NADPH Oxidase 1.
A. T. Comstock, S. Ganesan, A. Chattoraj, A. N. Faris, B. L. Margolis, M. B. Hershenson, and U. S. Sajjan (2011)
J. Virol. 85, 6795-6808
   Abstract »    Full Text »    PDF »
Guanine nucleotide exchange factor Vav1 regulates perivascular homing and bone marrow retention of hematopoietic stem and progenitor cells.
A. Sanchez-Aguilera, Y.-J. Lee, C. Lo Celso, F. Ferraro, K. Brumme, S. Mondal, C. Kim, A. Dorrance, H. R. Luo, D. T. Scadden, et al. (2011)
PNAS 108, 9607-9612
   Abstract »    Full Text »    PDF »
ROP GTPases Act with the Receptor-Like Protein PAN1 to Polarize Asymmetric Cell Division in Maize.
J. A. Humphries, Z. Vejlupkova, A. Luo, R. B. Meeley, A. W. Sylvester, J. E. Fowler, and L. G. Smith (2011)
PLANT CELL 23, 2273-2284
   Abstract »    Full Text »    PDF »
Novel Role of Rac1/WAVE Signaling Mechanism in Regulation of the Epithelial Na+ Channel.
A. V. Karpushev, V. Levchenko, D. V. Ilatovskaya, T. S. Pavlov, and A. Staruschenko (2011)
Hypertension 57, 996-1002
   Abstract »    Full Text »    PDF »
Targeting p21-activated kinase 1 (PAK1) to induce apoptosis of tumor cells.
C. C. Ong, A. M. Jubb, P. M. Haverty, W. Zhou, V. Tran, T. Truong, H. Turley, T. O'Brien, D. Vucic, A. L. Harris, et al. (2011)
PNAS 108, 7177-7182
   Abstract »    Full Text »    PDF »
An ezrin-rich, rigid uropod-like structure directs movement of amoeboid blebbing cells.
A. Lorentzen, J. Bamber, A. Sadok, I. Elson-Schwab, and C. J. Marshall (2011)
J. Cell Sci. 124, 1256-1267
   Abstract »    Full Text »    PDF »
Sphingomyelin upregulation in mature neurons contributes to TrkB activity by Rac1 endocytosis.
L. Trovo, P. P. Van Veldhoven, M. G. Martin, and C. G. Dotti (2011)
J. Cell Sci. 124, 1308-1315
   Abstract »    Full Text »    PDF »
Evidence That the Lipid Phosphatase SHIP-1 Regulates T Lymphocyte Morphology and Motility.
S. J. Harris, R. V. Parry, J. G. Foster, M. D. Blunt, A. Wang, F. Marelli-Berg, J. Westwick, and S. G. Ward (2011)
J. Immunol. 186, 4936-4945
   Abstract »    Full Text »    PDF »
Follicular Fluid High-Density Lipoprotein-Associated Sphingosine 1-Phosphate (S1P) Promotes Human Granulosa Lutein Cell Migration via S1P Receptor Type 3 and Small G-Protein RAC1.
S. Becker, S. von Otte, H. Robenek, K. Diedrich, and J.-R. Nofer (2011)
Biol Reprod 84, 604-612
   Abstract »    Full Text »    PDF »
TLR2-dependent pathway of heterologous down-modulation for the CC chemokine receptors 1, 2, and 5 in human blood monocytes.
J. M. Fox, E. Letellier, C. J. Oliphant, and N. Signoret (2011)
Blood 117, 1851-1860
   Abstract »    Full Text »    PDF »
Enforced hematopoietic cell E- and L-selectin ligand (HCELL) expression primes transendothelial migration of human mesenchymal stem cells.
S. P. Thankamony and R. Sackstein (2011)
PNAS 108, 2258-2263
   Abstract »    Full Text »    PDF »
Active Rac1 improves pathologic VEGF neovessel architecture and reduces vascular leak: mechanistic similarities with angiopoietin-1.
M. V. Hoang, J. A. Nagy, and D. R. Senger (2011)
Blood 117, 1751-1760
   Abstract »    Full Text »    PDF »
Deletion of ABCA1 and ABCG1 Impairs Macrophage Migration Because of Increased Rac1 Signaling.
T. A. Pagler, M. Wang, M. Mondal, A. J. Murphy, M. Westerterp, K. J. Moore, F. R. Maxfield, and A. R. Tall (2011)
Circ. Res. 108, 194-200
   Abstract »    Full Text »    PDF »
Phagocyte-like NADPH oxidase promotes cytokine-induced mitochondrial dysfunction in pancreatic {beta}-cells: evidence for regulation by Rac1.
W. Subasinghe, I. Syed, and A. Kowluru (2011)
Am J Physiol Regulatory Integrative Comp Physiol 300, R12-R20
   Abstract »    Full Text »    PDF »
The Rac1/JNK pathway is critical for EGFR-dependent barrier formation in human airway epithelial cells.
M. Terakado, Y. Gon, A. Sekiyama, I. Takeshita, Y. Kozu, K. Matsumoto, N. Takahashi, and S. Hashimoto (2011)
Am J Physiol Lung Cell Mol Physiol 300, L56-L63
   Abstract »    Full Text »    PDF »
Plexin-A4-semaphorin 3A signaling is required for Toll-like receptor- and sepsis-induced cytokine storm.
H. Wen, Y. Lei, S.-Y. Eun, and J. P.-Y. Ting (2010)
J. Exp. Med. 207, 2943-2957
   Abstract »    Full Text »    PDF »
Aberrant Overexpression of the Rgl2 Ral Small GTPase-specific Guanine Nucleotide Exchange Factor Promotes Pancreatic Cancer Growth through Ral-dependent and Ral-independent Mechanisms.
D. Vigil, T. D. Martin, F. Williams, J. J. Yeh, S. L. Campbell, and C. J. Der (2010)
J. Biol. Chem. 285, 34729-34740
   Abstract »    Full Text »    PDF »
Dact2 is expressed in the developing ureteric bud/collecting duct system of the kidney and controls morphogenetic behavior of collecting duct cells.
W.-C. Lee, M. T. Hough, W. Liu, R. Ekiert, N. O. Lindstrom, P. Hohenstein, and J. A. Davies (2010)
Am J Physiol Renal Physiol 299, F740-F751
   Abstract »    Full Text »    PDF »
Matrix Metalloproteinase-9 Is Upregulated in Nucleophosmin-Anaplastic Lymphoma Kinase-Positive Anaplastic Lymphomas and Activated at the Cell Surface by the Chaperone Heat Shock Protein 90 to Promote Cell Invasion.
F. Lagarrigue, S. Dupuis-Coronas, D. Ramel, G. Delsol, H. Tronchere, B. Payrastre, and F. Gaits-Iacovoni (2010)
Cancer Res. 70, 6978-6987
   Abstract »    Full Text »    PDF »
The mechanism by which RhoA regulates vascular reactivity after hemorrhagic shock in rats.
T. Li, Y. Fang, G. Yang, Y. Zhu, J. Xu, and L. Liu (2010)
Am J Physiol Heart Circ Physiol 299, H292-H299
   Abstract »    Full Text »    PDF »
ADP-Ribosylation Factor 6 Regulates Mammalian Myoblast Fusion through Phospholipase D1 and Phosphatidylinositol 4,5-Bisphosphate Signaling Pathways.
A.-S. Bach, S. Enjalbert, F. Comunale, S. Bodin, N. Vitale, S. Charrasse, and C. Gauthier-Rouviere (2010)
Mol. Biol. Cell 21, 2412-2424
   Abstract »    Full Text »    PDF »
Sitagliptin (MK0431) Inhibition of Dipeptidyl Peptidase IV Decreases Nonobese Diabetic Mouse CD4+ T-Cell Migration Through Incretin-Dependent and -Independent Pathways.
S.-J. Kim, C. Nian, and C. H. S. McIntosh (2010)
Diabetes 59, 1739-1750
   Abstract »    Full Text »    PDF »
Scaffold Proteins IRSp53 and Spinophilin Regulate Localized Rac Activation by T-lymphocyte Invasion and Metastasis Protein 1 (TIAM1).
S. Rajagopal, Y. Ji, K. Xu, Y. Li, K. Wicks, J. Liu, K. W. Wong, I. M. Herman, R. R. Isberg, and R. J. Buchsbaum (2010)
J. Biol. Chem. 285, 18060-18071
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882