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.


Logo for

Mol. Cell. Biol. 23 (5): 1534-1545

Copyright © 2003 by the American Society for Microbiology. All rights reserved.

Inhibitory and Stimulatory Regulation of Rac and Cell Motility by the G12/13-Rho and Gi Pathways Integrated Downstream of a Single G Protein-Coupled Sphingosine-1-Phosphate Receptor Isoform

Naotoshi Sugimoto, Noriko Takuwa, Hiroyuki Okamoto, Sotaro Sakurada, and Yoh Takuwa*

Department of Physiology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa 920-8640, Japan,

Received for publication 19 August 2002. Revision received 8 October 2002. Accepted for publication 6 December 2002.

Abstract: The G protein-coupled receptors S1P2/Edg5 and S1P3/Edg3 both mediate sphingosine-1-phosphate (S1P) stimulation of Rho, yet S1P2 but not S1P3 mediates downregulation of Rac activation, membrane ruffling, and cell migration in response to chemoattractants. Specific inhibition of endogenous G{alpha}12 and G{alpha}13, but not of G{alpha}q, by expression of respective C-terminal peptides abolished S1P2-mediated inhibition of Rac, membrane ruffling, and migration, as well as stimulation of Rho and stress fiber formation. Fusion receptors comprising S1P2 and either G{alpha}12 or G{alpha}13, but not G{alpha}q, mediated S1P stimulation of Rho and also inhibition of Rac and migration. Overexpression of G{alpha}i, by contrast, specifically antagonized S1P2-mediated inhibition of Rac and migration. The S1P2 actions were mimicked by expression of V14Rho and were abolished by C3 toxin and N19Rho, but not Rho kinase inhibitors. In contrast to S1P2, S1P3 mediated S1P-directed, pertussis toxin-sensitive chemotaxis and Rac activation despite concurrent stimulation of Rho via G12/13. Upon inactivation of Gi by pertussis toxin, S1P3 mediated inhibition of Rac and migration just like S1P2. These results indicate that integration of counteracting signals from the Gi- and the G12/13-Rho pathways directs either positive or negative regulation of Rac, and thus cell migration, upon activation of a single S1P receptor isoform.

* Corresponding author. Mailing address: Department of Physiology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan. Phone: 81-76-265-2165. Fax: 81-76-234-4223. E-mail: ytakuwa{at}

Sphingosine 1-phosphate signalling.
K. Mendelson, T. Evans, and T. Hla (2014)
Development 141, 5-9
   Abstract »    Full Text »    PDF »
PLC{varepsilon}, PKD1, and SSH1L Transduce RhoA Signaling to Protect Mitochondria from Oxidative Stress in the Heart.
S. Y. Xiang, K. Ouyang, B. S. Yung, S. Miyamoto, A. V. Smrcka, J. Chen, and J. H. Brown (2013)
Science Signaling 6, ra108
   Abstract »    Full Text »    PDF »
The G protein-coupled receptor GPRC5B contributes to neurogenesis in the developing mouse neocortex.
N. Kurabayashi, M. D. Nguyen, and K. Sanada (2013)
Development 140, 4335-4346
   Abstract »    Full Text »    PDF »
Soluble Guanylate Cyclase Generation of cGMP Regulates Migration of MGE Neurons.
S. Mandal, A. Stanco, E. S. Buys, G. Enikolopov, and J. L. R. Rubenstein (2013)
J. Neurosci. 33, 16897-16914
   Abstract »    Full Text »    PDF »
Cytokine IL-6 secretion by trophoblasts regulated via sphingosine-1-phosphate receptor 2 involving Rho/Rho-kinase and Rac1 signaling pathways.
P. Goyal, D. Brunnert, J. Ehrhardt, M. Bredow, S. Piccenini, and M. Zygmunt (2013)
Mol. Hum. Reprod. 19, 528-538
   Abstract »    Full Text »    PDF »
Essential Role of Class II Phosphatidylinositol-3-kinase-C2{alpha} in Sphingosine 1-Phosphate Receptor-1-mediated Signaling and Migration in Endothelial Cells.
K. Biswas, K. Yoshioka, K. Asanuma, Y. Okamoto, N. Takuwa, T. Sasaki, and Y. Takuwa (2013)
J. Biol. Chem. 288, 2325-2339
   Abstract »    Full Text »    PDF »
Lipid Phosphate Phosphatase 3 Negatively Regulates Smooth Muscle Cell Phenotypic Modulation to Limit Intimal Hyperplasia.
M. Panchatcharam, S. Miriyala, A. Salous, J. Wheeler, A. Dong, P. Mueller, M. Sunkara, D. Escalante-Alcalde, A. J. Morris, and S. S. Smyth (2013)
Arterioscler Thromb Vasc Biol 33, 52-59
   Abstract »    Full Text »    PDF »
Sphingosine-1-Phosphate Receptor 3 Promotes Neointimal Hyperplasia in Mouse Iliac-Femoral Arteries.
T. Shimizu, A. De Wispelaere, M. Winkler, T. D'Souza, J. Caylor, L. Chen, F. Dastvan, J. Deou, A. Cho, A. Larena-Avellaneda, et al. (2012)
Arterioscler Thromb Vasc Biol 32, 955-961
   Abstract »    Full Text »    PDF »
Sphingosine 1-Phosphate-Induced Motility and Endocytosis of Dendritic Cells Is Regulated by SWAP-70 through RhoA.
C. Ocana-Morgner, P. Reichardt, M. Chopin, S. Braungart, C. Wahren, M. Gunzer, and R. Jessberger (2011)
J. Immunol. 186, 5345-5355
   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 »
Genetic Evidence for Antagonism Between Pak Protein Kinase and Rho1 Small GTPase Signaling in Regulation of the Actin Cytoskeleton During Drosophila Oogenesis.
S. Vlachos and N. Harden (2011)
Genetics 187, 501-512
   Abstract »    Full Text »    PDF »
Mitogenic Signaling by the gep Oncogene Involves the Upregulation of S-Phase Kinase-Associated Protein 2.
R. Radhakrishnan, J. H. Ha, and D. N. Dhanasekaran (2010)
Genes & Cancer 1, 1033-1043
   Abstract »    Full Text »    PDF »
Sphingosine 1-Phosphate Receptor 2 Signals Through Leukemia-Associated RhoGEF (LARG), to Promote Smooth Muscle Cell Differentiation.
M. D. Medlin, D. P. Staus, A. D. Dubash, J. M. Taylor, and C. P. Mack (2010)
Arterioscler Thromb Vasc Biol 30, 1779-1786
   Abstract »    Full Text »    PDF »
Four-and-a-Half LIM Domain Protein 2 Is a Novel Regulator of Sphingosine 1-Phosphate Receptor 1 in CCL19-Induced Dendritic Cell Migration.
K. Konig, L. Diehl, U. Rommerscheidt-Fuss, C. Golletz, T. Quast, P. Kahl, W. Kolanus, P. Knolle, R. Buettner, and L. C. Heukamp (2010)
J. Immunol. 185, 1466-1475
   Abstract »    Full Text »    PDF »
Sphingosine 1-Phosphate (S1P) Regulates Vascular Contraction via S1P3 Receptor: Investigation Based on a New S1P3 Receptor Antagonist.
A. Murakami, H. Takasugi, S. Ohnuma, Y. Koide, A. Sakurai, S. Takeda, T. Hasegawa, J. Sasamori, T. Konno, K. Hayashi, et al. (2010)
Mol. Pharmacol. 77, 704-713
   Abstract »    Full Text »    PDF »
Inhibitory Role of Sphingosine 1-Phosphate Receptor 2 in Macrophage Recruitment during Inflammation.
J. Michaud, D.-S. Im, and T. Hla (2010)
J. Immunol. 184, 1475-1483
   Abstract »    Full Text »    PDF »
S1P2, the G Protein-Coupled Receptor for Sphingosine-1-Phosphate, Negatively Regulates Tumor Angiogenesis and Tumor Growth In vivo in Mice.
W. Du, N. Takuwa, K. Yoshioka, Y. Okamoto, K. Gonda, K. Sugihara, A. Fukamizu, M. Asano, and Y. Takuwa (2010)
Cancer Res. 70, 772-781
   Abstract »    Full Text »    PDF »
Role of Rap1B and Tumor Suppressor PTEN in the Negative Regulation of Lysophosphatidic Acid--induced Migration by Isoproterenol in Glioma Cells.
E. Malchinkhuu, K. Sato, T. Maehama, S. Ishiuchi, Y. Yoshimoto, C. Mogi, T. Kimura, H. Kurose, H. Tomura, and F. Okajima (2009)
Mol. Biol. Cell 20, 5156-5165
   Abstract »    Full Text »    PDF »
Sphingosine 1-Phosphate: A Regulator of Arterial Lesions.
G. Daum, A. Grabski, and M. A. Reidy (2009)
Arterioscler Thromb Vasc Biol 29, 1439-1443
   Abstract »    Full Text »    PDF »
Regulation of vascular physiology and pathology by the S1P2 receptor subtype.
A. Skoura and T. Hla (2009)
Cardiovasc Res 82, 221-228
   Abstract »    Full Text »    PDF »
Sphingosine-1-phosphate and sphingosine kinase are critical for transforming growth factor-{beta}-stimulated collagen production by cardiac fibroblasts.
N. Gellings Lowe, J. S. Swaney, K. M. Moreno, and R. A. Sabbadini (2009)
Cardiovasc Res 82, 303-312
   Abstract »    Full Text »    PDF »
LPA1 receptors mediate stimulation, whereas LPA2 receptors mediate inhibition, of migration of pancreatic cancer cells in response to lysophosphatidic acid and malignant ascites.
M. Komachi, H. Tomura, E. Malchinkhuu, M. Tobo, C. Mogi, T. Yamada, T. Kimura, A. Kuwabara, H. Ohta, D.-S. Im, et al. (2009)
Carcinogenesis 30, 457-465
   Abstract »    Full Text »    PDF »
Balance of S1P1 and S1P2 signaling regulates peripheral microvascular permeability in rat cremaster muscle vasculature.
J.-F. Lee, S. Gordon, R. Estrada, L. Wang, D. L. Siow, B. W. Wattenberg, D. Lominadze, and M.-J. Lee (2009)
Am J Physiol Heart Circ Physiol 296, H33-H42
   Abstract »    Full Text »    PDF »
Antagonism of Sphingosine 1-Phosphate Receptor-2 Enhances Migration of Neural Progenitor Cells Toward an Area of Brain Infarction * Supplemental Materials and Methods.
A. Kimura, T. Ohmori, Y. Kashiwakura, R. Ohkawa, S. Madoiwa, J. Mimuro, K. Shimazaki, Y. Hoshino, Y. Yatomi, and Y. Sakata (2008)
Stroke 39, 3411-3417
   Abstract »    Full Text »    PDF »
Role of LPA4/p2y9/GPR23 in Negative Regulation of Cell Motility.
Z. Lee, C.-T. Cheng, H. Zhang, M. A. Subler, J. Wu, A. Mukherjee, J. J. Windle, C.-K. Chen, and X. Fang (2008)
Mol. Biol. Cell 19, 5435-5445
   Abstract »    Full Text »    PDF »
Up-regulating Sphingosine 1-Phosphate Receptor-2 Signaling Impairs Chemotactic, Wound-healing, and Morphogenetic Responses in Senescent Endothelial Cells.
R. Estrada, Q. Zeng, H. Lu, H. Sarojini, J.-F. Lee, S. P. Mathis, T. Sanchez, E. Wang, C. D. Kontos, C.-Y. Lin, et al. (2008)
J. Biol. Chem. 283, 30363-30375
   Abstract »    Full Text »    PDF »
Filamin A Links Sphingosine Kinase 1 and Sphingosine-1-Phosphate Receptor 1 at Lamellipodia To Orchestrate Cell Migration.
M. Maceyka, S. E. Alvarez, S. Milstien, and S. Spiegel (2008)
Mol. Cell. Biol. 28, 5687-5697
   Abstract »    Full Text »    PDF »
G12/13 and Gq mediate S1P2-induced inhibition of Rac and migration in vascular smooth muscle in a manner dependent on Rho but not Rho kinase.
S.-i. Takashima, N. Sugimoto, N. Takuwa, Y. Okamoto, K. Yoshioka, M. Takamura, S. Takata, S. Kaneko, and Y. Takuwa (2008)
Cardiovasc Res 79, 689-697
   Abstract »    Full Text »    PDF »
Apoptosis induces expression of sphingosine kinase 1 to release sphingosine-1-phosphate as a "come-and-get-me" signal.
D. R. Gude, S. E. Alvarez, S. W. Paugh, P. Mitra, J. Yu, R. Griffiths, S. E. Barbour, S. Milstien, and S. Spiegel (2008)
FASEB J 22, 2629-2638
   Abstract »    Full Text »    PDF »
HDL-Associated Lysosphingolipids Inhibit NAD(P)H Oxidase-Dependent Monocyte Chemoattractant Protein-1 Production.
M. Tolle, A. Pawlak, M. Schuchardt, A. Kawamura, U. J. Tietge, S. Lorkowski, P. Keul, G. Assmann, J. Chun, B. Levkau, et al. (2008)
Arterioscler Thromb Vasc Biol 28, 1542-1548
   Abstract »    Full Text »    PDF »
Sphingosine-1-Phosphate Receptor Subtypes Differentially Regulate Smooth Muscle Cell Phenotype.
B. R. Wamhoff, K. R. Lynch, T. L. Macdonald, and G. K. Owens (2008)
Arterioscler Thromb Vasc Biol 28, 1454-1461
   Abstract »    Full Text »    PDF »
S1P differentially regulates migration of human ovarian cancer and human ovarian surface epithelial cells.
D. Wang, Z. Zhao, A. Caperell-Grant, G. Yang, S. C. Mok, J. Liu, R. M. Bigsby, and Y. Xu (2008)
Mol. Cancer Ther. 7, 1993-2002
   Abstract »    Full Text »    PDF »
Distinguishing fibroblast promigratory and procontractile growth factor environments in 3-D collagen matrices.
H. Jiang, S. Rhee, C.-H. Ho, and F. Grinnell (2008)
FASEB J 22, 2151-2160
   Abstract »    Full Text »    PDF »
Sphingosine Kinases and Sphingosine-1-Phosphate Are Critical for Transforming Growth Factor {beta}-Induced Extracellular Signal-Regulated Kinase 1 and 2 Activation and Promotion of Migration and Invasion of Esophageal Cancer Cells.
A. V. Miller, S. E. Alvarez, S. Spiegel, and D. A. Lebman (2008)
Mol. Cell. Biol. 28, 4142-4151
   Abstract »    Full Text »    PDF »
"Inside-Out" Signaling of Sphingosine-1-Phosphate: Therapeutic Targets.
K. Takabe, S. W. Paugh, S. Milstien, and S. Spiegel (2008)
Pharmacol. Rev. 60, 181-195
   Abstract »    Full Text »    PDF »
PDZRhoGEF and myosin II localize RhoA activity to the back of polarizing neutrophil-like cells.
K. Wong, A. Van Keymeulen, and H. R. Bourne (2007)
J. Cell Biol. 179, 1141-1148
   Abstract »    Full Text »    PDF »
Sphingosine 1-Phosphate Receptor 2 Negatively Regulates Neointimal Formation in Mouse Arteries.
T. Shimizu, T. Nakazawa, A. Cho, F. Dastvan, D. Shilling, G. Daum, and M. A. Reidy (2007)
Circ. Res. 101, 995-1000
   Abstract »    Full Text »    PDF »
Identification of an alternative G{alpha}q-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes.
G. Shi, S. Partida-Sanchez, R. S. Misra, M. Tighe, M. T. Borchers, J. J. Lee, M. I. Simon, and F. E. Lund (2007)
J. Exp. Med. 204, 2705-2718
   Abstract »    Full Text »    PDF »
Oligodendrocyte Lineage Transcription Factor 2 Inhibits the Motility of a Human Glial Tumor Cell Line by Activating RhoA.
K. Tabu, Y. Ohba, T. Suzuki, Y. Makino, T. Kimura, A. Ohnishi, M. Sakai, T. Watanabe, S. Tanaka, and H. Sawa (2007)
Mol. Cancer Res. 5, 1099-1109
   Abstract »    Full Text »    PDF »
Control of nuclear centration in the C. elegans zygote by receptor-independent G{alpha} signaling and myosin II.
M. B. Goulding, J. C. Canman, E. N. Senning, A. H. Marcus, and B. Bowerman (2007)
J. Cell Biol. 178, 1177-1191
   Abstract »    Full Text »    PDF »
Ovarian Cancer G Protein Coupled Receptor 1, a New Metastasis Suppressor Gene in Prostate Cancer.
L. S. Singh, M. Berk, R. Oates, Z. Zhao, H. Tan, Y. Jiang, A. Zhou, K. Kirmani, R. Steinmetz, D. Lindner, et al. (2007)
J Natl Cancer Inst 99, 1313-1327
   Abstract »    Full Text »    PDF »
Induction of Vascular Permeability by the Sphingosine-1-Phosphate Receptor-2 (S1P2R) and its Downstream Effectors ROCK and PTEN.
T. Sanchez, A. Skoura, M. T. Wu, B. Casserly, E. O. Harrington, and T. Hla (2007)
Arterioscler Thromb Vasc Biol 27, 1312-1318
   Abstract »    Full Text »    PDF »
Sphingosine-1-phosphate receptor expression in cardiac fibroblasts is modulated by in vitro culture conditions.
L. K. Landeen, N. Aroonsakool, J. H. Haga, B. S. Hu, and W. R. Giles (2007)
Am J Physiol Heart Circ Physiol 292, H2698-H2711
   Abstract »    Full Text »    PDF »
Activation of sphingosine-1-phosphate receptor S1P5 inhibits oligodendrocyte progenitor migration.
A. S. Novgorodov, M. El-Alwani, J. Bielawski, L. M. Obeid, and T. I. Gudz (2007)
FASEB J 21, 1503-1514
   Abstract »    Full Text »    PDF »
Role of lipoprotein-associated lysophospholipids in migratory activity of coronary artery smooth muscle cells.
A. Damirin, H. Tomura, M. Komachi, J.-P. Liu, C. Mogi, M. Tobo, J.-Q. Wang, T. Kimura, A. Kuwabara, Y. Yamazaki, et al. (2007)
Am J Physiol Heart Circ Physiol 292, H2513-H2522
   Abstract »    Full Text »    PDF »
Identification of the Intracellular Region of the Leukotriene B4 Receptor Type 1 That Is Specifically Involved in Gi Activation.
K. Kuniyeda, T. Okuno, K. Terawaki, M. Miyano, T. Yokomizo, and T. Shimizu (2007)
J. Biol. Chem. 282, 3998-4006
   Abstract »    Full Text »    PDF »
Characterization of S1P1 and S1P2 receptor function in smooth muscle by receptor silencing and receptor protection.
W. Hu, S. Mahavadi, J. Huang, F. Li, and K. S. Murthy (2006)
Am J Physiol Gastrointest Liver Physiol 291, G605-G610
   Abstract »    Full Text »    PDF »
To stabilize neutrophil polarity, PIP3 and Cdc42 augment RhoA activity at the back as well as signals at the front.
A. Van Keymeulen, K. Wong, Z. A. Knight, C. Govaerts, K. M. Hahn, K. M. Shokat, and H. R. Bourne (2006)
J. Cell Biol. 174, 437-445
   Abstract »    Full Text »    PDF »
The G12 Family of G Proteins as a Reporter of Thromboxane A2 Receptor Activity.
L. Zhang, C. DiLizio, D. Kim, E. M. Smyth, and D. R. Manning (2006)
Mol. Pharmacol. 69, 1433-1440
   Abstract »    Full Text »    PDF »
Bring Your Own G Protein.
J. D. Hildebrandt (2006)
Mol. Pharmacol. 69, 1079-1082
   Abstract »    Full Text »    PDF »
5-Oxo-Eicosatetraenoic Acid-Induced Chemotaxis: Identification of a Responsible Receptor hGPCR48 and Negative Regulation by G Protein G12/13..
D. Koike, H. Obinata, A. Yamamoto, S. Takeda, H. Komori, F. Nara, T. Izumi, and T. Haga (2006)
J. Biochem. 139, 543-549
   Abstract »    Full Text »    PDF »
Mammalian G Proteins and Their Cell Type Specific Functions.
N. Wettschureck and S. Offermanns (2005)
Physiol Rev 85, 1159-1204
   Abstract »    Full Text »    PDF »
Role of Sphingosine Kinase 2 in Cell Migration toward Epidermal Growth Factor.
N. C. Hait, S. Sarkar, H. Le Stunff, A. Mikami, M. Maceyka, S. Milstien, and S. Spiegel (2005)
J. Biol. Chem. 280, 29462-29469
   Abstract »    Full Text »    PDF »
Sphingosine 1-Phosphate-Related Metabolism in the Blood Vessel.
S. Aoki, Y. Yatomi, M. Ohta, M. Osada, F. Kazama, K. Satoh, K. Nakahara, and Y. Ozaki (2005)
J. Biochem. 138, 47-55
   Abstract »    Full Text »    PDF »
G Protein-coupled Receptor Kinase 2-mediated Phosphorylation of Ezrin Is Required for G Protein-coupled Receptor-dependent Reorganization of the Actin Cytoskeleton.
S. H. Cant and J. A. Pitcher (2005)
Mol. Biol. Cell 16, 3088-3099
   Abstract »    Full Text »    PDF »
Essential roles of G{alpha}12/13 signaling in distinct cell behaviors driving zebrafish convergence and extension gastrulation movements.
F. Lin, D. S. Sepich, S. Chen, J. Topczewski, C. Yin, L. Solnica-Krezel, and H. Hamm (2005)
J. Cell Biol. 169, 777-787
   Abstract »    Full Text »    PDF »
The S1P2 Receptor Negatively Regulates Platelet-Derived Growth Factor-Induced Motility and Proliferation.
S. K. Goparaju, P. S. Jolly, K. R. Watterson, M. Bektas, S. Alvarez, S. Sarkar, L. Mel, I. Ishii, J. Chun, S. Milstien, et al. (2005)
Mol. Cell. Biol. 25, 4237-4249
   Abstract »    Full Text »    PDF »
The G Protein-Coupled Receptor S1P2 Regulates Rho/Rho Kinase Pathway to Inhibit Tumor Cell Migration.
D. Lepley, J.-H. Paik, T. Hla, and F. Ferrer (2005)
Cancer Res. 65, 3788-3795
   Abstract »    Full Text »    PDF »
PTEN as an effector in the signaling of antimigratory G protein-coupled receptor.
T. Sanchez, S. Thangada, M.-T. Wu, C. D. Kontos, D. Wu, H. Wu, and T. Hla (2005)
PNAS 102, 4312-4317
   Abstract »    Full Text »    PDF »
Overlapping Signaling Pathways of Sphingosine 1-Phosphate and TGF-{beta} in the Murine Langerhans Cell Line XS52.
H. H. Radeke, H. von Wenckstern, K. Stoidtner, B. Sauer, S. Hammer, and B. Kleuser (2005)
J. Immunol. 174, 2778-2786
   Abstract »    Full Text »    PDF »
Sphingosine 1-Phosphate Stimulates Smooth Muscle Cell Differentiation and Proliferation by Activating Separate Serum Response Factor Co-factors.
K. Lockman, J. S. Hinson, M. D. Medlin, D. Morris, J. M. Taylor, and C. P. Mack (2004)
J. Biol. Chem. 279, 42422-42430
   Abstract »    Full Text »    PDF »
Sphingosine 1-Phosphate Cross-activates the Smad Signaling Cascade and Mimics Transforming Growth Factor-{beta}-induced Cell Responses.
C. Xin, S. Ren, B. Kleuser, S. Shabahang, W. Eberhardt, H. Radeke, M. Schafer-Korting, J. Pfeilschifter, and A. Huwiler (2004)
J. Biol. Chem. 279, 35255-35262
   Abstract »    Full Text »    PDF »
Role of Sphingosine-1-phosphate Phosphatase 1 in Epidermal Growth Factor-induced Chemotaxis.
H. Le Stunff, A. Mikami, P. Giussani, J. P Hobson, P. S. Jolly, S. Milstien, and S. Spiegel (2004)
J. Biol. Chem. 279, 34290-34297
   Abstract »    Full Text »    PDF »
Transactivation of Sphingosine-1-Phosphate Receptors by Fc{varepsilon}RI Triggering Is Required for Normal Mast Cell Degranulation and Chemotaxis.
P. S. Jolly, M. Bektas, A. Olivera, C. Gonzalez-Espinosa, R. L. Proia, J. Rivera, S. Milstien, and S. Spiegel (2004)
J. Exp. Med. 199, 959-970
   Abstract »    Full Text »    PDF »
Point-Counterpoint of Sphingosine 1-Phosphate Metabolism.
J. D. Saba and T. Hla (2004)
Circ. Res. 94, 724-734
   Abstract »    Full Text »    PDF »
Blood Lipid Mediator Sphingosine 1-Phosphate Potently Stimulates Platelet-derived Growth Factor-A and -B Chain Expression through S1P1-Gi-Ras-MAPK-dependent Induction of Kruppel-like Factor 5.
S. Usui, N. Sugimoto, N. Takuwa, S. Sakagami, S. Takata, S. Kaneko, and Y. Takuwa (2004)
J. Biol. Chem. 279, 12300-12311
   Abstract »    Full Text »    PDF »
The Tumor Invasion Inhibitor Dihydromotuporamine C Activates RHO, Remodels Stress Fibers and Focal Adhesions, and Stimulates Sodium-Proton Exchange.
L. M. McHardy, R. Sinotte, A. Troussard, C. Sheldon, J. Church, D. E. Williams, R. J. Andersen, S. Dedhar, M. Roberge, and C. D. Roskelley (2004)
Cancer Res. 64, 1468-1474
   Abstract »    Full Text »    PDF »
The Ca2+-sensing receptor couples to G{alpha}12/13 to activate phospholipase D in Madin-Darby canine kidney cells.
C. Huang, K. M. Hujer, Z. Wu, and R. T. Miller (2004)
Am J Physiol Cell Physiol 286, C22-C30
   Abstract »    Full Text »    PDF »
Ligand-dependent Inhibition of B16 Melanoma Cell Migration and Invasion via Endogenous S1P2 G Protein-coupled Receptor: REQUIREMENT OF INHIBITION OF CELLULAR RAC ACTIVITY.
K. Arikawa, N. Takuwa, H. Yamaguchi, N. Sugimoto, J. Kitayama, H. Nagawa, K. Takehara, and Y. Takuwa (2003)
J. Biol. Chem. 278, 32841-32851
   Abstract »    Full Text »    PDF »
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.
T. M. Eisenhaure, S. A. Francis, L. D. Willison, S. R. Coughlin, and D. J. Lerner (2003)
J. Biol. Chem. 278, 30975-30984
   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