The 'invisible hand': regulation of RHO GTPases by RHOGDIs (original) (raw)
DerMardirossian, C. & Bokoch, G. M. GDIs: central regulatory molecules in Rho GTPase activation. Trends Cell Biol.15, 356–363 (2005). ArticleCASPubMed Google Scholar
Fukumoto, Y. et al. Molecular cloning and characterization of a novel type of regulatory protein (GDI) for the rho proteins, ras p21-like small GTP-binding proteins. Oncogene5, 1321–1328 (1990). CASPubMed Google Scholar
Leonard, D. et al. The identification and characterization of a GDP-dissociation inhibitor (GDI) for the CDC42Hs protein. J. Biol. Chem.267, 22860–22868 (1992). ArticleCASPubMed Google Scholar
Lelias, J. M. et al. cDNA cloning of a human mRNA preferentially expressed in hematopoietic cells and with homology to a GDP-dissociation inhibitor for the rho GTP-binding proteins. Proc. Natl Acad. Sci. USA90, 1479–1483 (1993). ArticleCASPubMedPubMed Central Google Scholar
Scherle, P., Behrens, T. & Staudt, L. M. Ly-GDI, a GDP-dissociation inhibitor of the RhoA GTP-binding protein, is expressed preferentially in lymphocytes. Proc. Natl Acad. Sci. USA90, 7568–7572 (1993). ArticleCASPubMedPubMed Central Google Scholar
Platko, J. V. et al. A single residue can modify target-binding affinity and activity of the functional domain of the Rho-subfamily GDP dissociation inhibitors. Proc. Natl Acad. Sci. USA92, 2974–2978 (1995). ArticleCASPubMedPubMed Central Google Scholar
Gorvel, J. P., Chang, T. C., Boretto, J., Azuma, T. & Chavrier, P. Differential properties of D4/LyGDI versus RhoGDI: phosphorylation and rho GTPase selectivity. FEBS Lett.422, 269–273 (1998). ArticleCASPubMed Google Scholar
Brunet, N., Morin, A. & Olofsson, B. RhoGDI-3 regulates RhoG and targets this protein to the Golgi complex through its unique N-terminal domain. Traffic3, 342–357 (2002). ArticleCASPubMed Google Scholar
Zalcman, G. et al. RhoGDI-3 is a new GDP dissociation inhibitor (GDI). Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG. J. Biol. Chem.271, 30366–30374 (1996). ArticleCASPubMed Google Scholar
Adra, C. N. et al. RhoGDIγ: a GDP-dissociation inhibitor for Rho proteins with preferential expression in brain and pancreas. Proc. Natl Acad. Sci. USA94, 4279–4284 (1997). ArticleCASPubMedPubMed Central Google Scholar
Smith, A. The Theory of Moral Sentiments (A. Millar, London, 1759). Book Google Scholar
Boulter, E. et al. Regulation of Rho GTPase crosstalk, degradation and activity by RhoGDI1. Nature Cell Biol.12, 477–483 (2010). Shows that RHOGDI1 not only does act as a chaperone, protecting multiple RHO GTPases from proteolytic degradation, but is also involved in the crosstalk of RHO GTPases, which compete for binding to RHOGDI1, such that overexpression of one leads to the displacement and degradation of the others. ArticleCASPubMed Google Scholar
Ueda, T., Kikuchi, A., Ohga, N., Yamamoto, J. & Takai, Y. Purification and characterization from bovine brain cytosol of a novel regulatory protein inhibiting the dissociation of GDP from and the subsequent binding of GTP to rhoB p20, a ras p21-like GTP-binding protein. J. Biol. Chem.265, 9373–9380 (1990). ArticleCASPubMed Google Scholar
Hart, M. J. et al. A GDP dissociation inhibitor that serves as a GTPase inhibitor for the Ras-like protein CDC42Hs. Science258, 812–815 (1992). ArticleCASPubMed Google Scholar
Ren, X. D., Kiosses, W. B. & Schwartz, M. A. Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton. EMBO J.18, 578–585 (1999). ArticleCASPubMedPubMed Central Google Scholar
Cox, A. D. & Der, C. J. Protein prenylation: more than just glue? Curr. Opin. Cell Biol.4, 1008–1016 (1992). ArticleCASPubMed Google Scholar
Rolli-Derkinderen, M. et al. Phosphorylation of serine 188 protects RhoA from ubiquitin/proteasome-mediated degradation in vascular smooth muscle cells. Circ. Res.96, 1152–1160 (2005). ArticleCASPubMed Google Scholar
Gandhi, P. N. et al. An activating mutant of Rac1 that fails to interact with Rho GDP-dissociation inhibitor stimulates membrane ruffling in mammalian cells. Biochem. J.378, 409–419 (2004). ArticleCASPubMedPubMed Central Google Scholar
Gibson, R. M. et al. An activating mutant of Cdc42 that fails to interact with Rho GDP-dissociation inhibitor localizes to the plasma membrane and mediates actin reorganization. Exp. Cell Res.301, 211–222 (2004). ArticleCASPubMed Google Scholar
Gibson, R. M. & Wilson-Delfosse, A. L. RhoGDI-binding-defective mutant of Cdc42Hs targets to membranes and activates filopodia formation but does not cycle with the cytosol of mammalian cells. Biochem. J.359, 285–294 (2001). ArticleCASPubMedPubMed Central Google Scholar
Tiedje, C., Sakwa, I., Just, U. & Hofken, T. The Rho GDI Rdi1 regulates Rho GTPases by distinct mechanisms. Mol. Biol. Cell19, 2885–2896 (2008). ArticleCASPubMedPubMed Central Google Scholar
Shibata, S. et al. Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease. Nature Med.14, 1370–1376 (2008). ArticleCASPubMed Google Scholar
Togawa, A. et al. Progressive impairment of kidneys and reproductive organs in mice lacking Rho GDIα. Oncogene18, 5373–5380 (1999). ArticleCASPubMed Google Scholar
Lin, Q., Fuji, R. N., Yang, W. & Cerione, R. A. RhoGDI is required for Cdc42-mediated cellular transformation. Curr. Biol.13, 1469–1479 (2003). ArticleCASPubMed Google Scholar
Lin, R., Bagrodia, S., Cerione, R. & Manor, D. A novel Cdc42Hs mutant induces cellular transformation. Curr. Biol.7, 794–797 (1997). ArticleCASPubMed Google Scholar
Chianale, F. et al. Diacylglycerol kinase α mediates HGF-induced Rac activation and membrane ruffling by regulating atypical PKC and RhoGDI. Proc. Natl Acad. Sci. USA107, 4182–4187 (2010). ArticleCASPubMedPubMed Central Google Scholar
Nevins, A. K. & Thurmond, D. C. Caveolin-1 functions as a novel Cdc42 guanine nucleotide dissociation inhibitor in pancreatic β-cells. J. Biol. Chem.281, 18961–18972 (2006). ArticleCASPubMed Google Scholar
Kowluru, A. et al. Glucose- and GTP-dependent stimulation of the carboxyl methylation of CDC42 in rodent and human pancreatic islets and pure β cells. Evidence for an essential role of GTP-binding proteins in nutrient-induced insulin secretion. J. Clin. Invest.98, 540–555 (1996). ArticleCASPubMedPubMed Central Google Scholar
Slaughter, B. D., Das, A., Schwartz, J. W., Rubinstein, B. & Li, R. Dual modes of Cdc42 recycling fine-tune polarized morphogenesis. Dev. Cell17, 823–835 (2009). Proposes a dual recycling mechanism for Cdc42 in yeast. ArticleCASPubMedPubMed Central Google Scholar
Pruyne, D. & Bretscher, A. Polarization of cell growth in yeast. I. Establishment and maintenance of polarity states. J. Cell Sci.113, 365–375 (2000). ArticleCASPubMed Google Scholar
Hoffman, G. R., Nassar, N. & Cerione, R. A. Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI. Cell100, 345–356 (2000). Solved the crystal structure of prenylated CDC42 in complex with RHOGDI1. ArticleCASPubMed Google Scholar
Longenecker, K. et al. How RhoGDI binds Rho. ActaCrystallogr. D Biol. Crystallogr.55, 1503–1515 (1999). ArticleCAS Google Scholar
Grizot, S. et al. Crystal structure of the Rac1–RhoGDI complex involved in NADPH oxidase activation. Biochemistry40, 10007–10013 (2001). ArticleCASPubMed Google Scholar
Scheffzek, K., Stephan, I., Jensen, O. N., Illenberger, D. & Gierschik, P. The Rac–RhoGDI complex and the structural basis for the regulation of Rho proteins by RhoGDI. Nature Struct. Biol.7, 122–126 (2000). ArticleCASPubMed Google Scholar
Nomanbhoy, T. K. & Cerione, R. Characterization of the interaction between RhoGDI and Cdc42Hs using fluorescence spectroscopy. J. Biol. Chem.271, 10004–10009 (1996). ArticleCASPubMed Google Scholar
Phillips, M. J., Calero, G., Chan, B., Ramachandran, S. & Cerione, R. A. Effector proteins exert an important influence on the signaling-active state of the small GTPase Cdc42. J. Biol. Chem.283, 14153–14164 (2008). ArticleCASPubMedPubMed Central Google Scholar
Johnson, J. L., Erickson, J. W. & Cerione, R. A. New insights into how the Rho guanine nucleotide dissociation inhibitor regulates the interaction of Cdc42 with membranes. J. Biol. Chem.284, 23860–23871 (2009). ArticleCASPubMedPubMed Central Google Scholar
Chuang, T. H., Bohl, B. P. & Bokoch, G. M. Biologically active lipids are regulators of Rac.GDI complexation. J. Biol. Chem.268, 26206–26211 (1993). ArticleCASPubMed Google Scholar
Faure, J., Vignais, P. V. & Dagher, M. C. Phosphoinositide-dependent activation of Rho A involves partial opening of the RhoA/Rho-GDI complex. Eur. J. Biochem.262, 879–889 (1999). ArticleCASPubMed Google Scholar
Del Pozo, M. A. et al. Integrins regulate Rac targeting by internalization of membrane domains. Science303, 839–842 (2004). ArticleCASPubMed Google Scholar
Del Pozo, M. A. et al. Integrins regulate GTP-Rac localized effector interactions through dissociation of Rho-GDI. Nature Cell Biol.4, 232–239 (2002). ArticleCASPubMed Google Scholar
Robbe, K., Otto-Bruc, A., Chardin, P. & Antonny, B. Dissociation of GDP dissociation inhibitor and membrane translocation are required for efficient activation of Rac by the Dbl homology-pleckstrin homology region of Tiam. J. Biol. Chem.278, 4756–4762 (2003). Provides evidence for a two-step model of RHO protein activation, in which release from RHOGDI is promoted by lipids, leading to membrane translocation and subsequent GEF-mediated nucleotide exchange. ArticleCASPubMed Google Scholar
Ugolev, Y., Berdichevsky, Y., Weinbaum, C. & Pick, E. Dissociation of Rac1(GDP).RhoGDI complexes by the cooperative action of anionic liposomes containing phosphatidylinositol 3,4,5-trisphosphate, Rac guanine nucleotide exchange factor, and GTP. J. Biol. Chem.283, 22257–22271 (2008). Shows that liposomes containing phosphoinositides cooperate with active GEFs to release and activate RAC1 from RHOGDI1. ArticleCASPubMedPubMed Central Google Scholar
Worthylake, D. K., Rossman, K. L. & Sondek, J. Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1. Nature408, 682–688 (2000). ArticleCASPubMed Google Scholar
Machner, M. P. & Isberg, R. R. A bifunctional bacterial protein links GDI displacement to Rab1 activation. Science318, 974–977 (2007). ArticleCASPubMed Google Scholar
Schoebel, S., Oesterlin, L. K., Blankenfeldt, W., Goody, R. S. & Itzen, A. RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity. Mol. Cell36, 1060–1072 (2009). ArticleCASPubMed Google Scholar
Kim, O., Yang, J. & Qiu, Y. Selective activation of small GTPase RhoA by tyrosine kinase Etk through its pleckstrin homology domain. J. Biol. Chem.277, 30066–30071 (2002). ArticleCASPubMed Google Scholar
Maeda, M., Matsui, T., Imamura, M. & Tsukita, S. Expression level, subcellular distribution and Rho-GDI binding affinity of merlin in comparison with ezrin/radixin/moesin proteins. Oncogene18, 4788–4797 (1999). ArticleCASPubMed Google Scholar
Takahashi, K. et al. Direct interaction of the Rho GDP dissociation inhibitor with ezrin/radixin/moesin initiates the activation of the Rho small G protein. J. Biol. Chem.272, 23371–23375 (1997). ArticleCASPubMed Google Scholar
Yamashita, T. & Tohyama, M. The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI. Nature Neurosci.6, 461–467 (2003). ArticleCASPubMed Google Scholar
Takahashi, K. et al. Interaction of radixin with Rho small G protein GDP/GTP exchange protein Dbl. Oncogene16, 3279–3284 (1998). ArticlePubMedCAS Google Scholar
Hirao, M. et al. Regulation mechanism of ERM (ezrin/radixin/moesin) protein/plasma membrane association: possible involvement of phosphatidylinositol turnover and Rho-dependent signaling pathway. J. Cell Biol.135, 37–51 (1996). ArticleCASPubMed Google Scholar
Qiu, Y. & Kung, H. J. Signaling network of the Btk family kinases. Oncogene19, 5651–5661 (2000). ArticleCASPubMed Google Scholar
DerMardirossian, C., Schnelzer, A. & Bokoch, G. M. Phosphorylation of RhoGDI by Pak1 mediates dissociation of Rac GTPase. Mol. Cell15, 117–127 (2004). Shows that RHOGDI1 is a substrate for PAK1 and that phosphorylation by PAK1 results in the selective release of RAC1 from RHOGDI1. ArticleCASPubMed Google Scholar
Dovas, A. et al. Serine34 phosphorylation of RHO guanine dissociation inhibitor (RHOGDIα) links signaling from conventional protein kinase C to RHO GTPase in cell adhesion. J. Biol. Chem.285, 23296–23308 (2010). ArticleCASPubMedPubMed Central Google Scholar
Abramovici, H. et al. Diacylglycerol kinase-ζ regulates actin cytoskeleton reorganization through dissociation of Rac1 from RhoGDI. Mol. Biol. Cell20, 2049–2059 (2009). Demonstrates that the phosphatidic acid produced by DGKζ initiates RHOGDI release and RAC1 activation through PAK1-mediated phosphorylation of RHOGDI. ArticleCASPubMedPubMed Central Google Scholar
Elfenbein, A. et al. Suppression of RhoG activity is mediated by a syndecan 4–synectin–RhoGDI1 complex and is reversed by PKCα in a Rac1 activation pathway. J. Cell Biol.186, 75–83 (2009). Shows that RHOG affinity for RHOGDI1 increases when RHOGDI forms a complex with syndecan 4 and its binding partner, synectin, and that, in response to FGF2 binding to syndecan 4, RHOG is released and activated as a result of phosphorylation by PKCα. ArticleCASPubMedPubMed Central Google Scholar
Brugnera, E. et al. Unconventional Rac-GEF activity is mediated through the Dock180–ELMO complex. Nature Cell Biol.4, 574–582 (2002). ArticleCASPubMed Google Scholar
Gumienny, T. L. et al. CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell107, 27–41 (2001). ArticleCASPubMed Google Scholar
Michaelson, D. et al. Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding. J. Cell Biol.152, 111–126 (2001). A seminal paper analyzing the factors that affect the subcellular distribution of RHO GTPases. ArticleCASPubMedPubMed Central Google Scholar
Rolli-Derkinderen, M., Toumaniantz, G., Pacaud, P. & Loirand, G. RhoA phosphorylation induces Rac1 release from guanine dissociation inhibitor α and stimulation of vascular smooth muscle cell migration. Mol. Cell. Biol.30, 4786–4796 (2010). Shows that RHOA phosphorylation by PKG in vascular smooth muscle cells increases RHOA binding to RHOGDI1, thereby displacing and activating bound RAC1, resulting in increased cell migration. ArticleCASPubMedPubMed Central Google Scholar
Tkachenko, E. et al. Protein kinase A governs a RhoA–RhoGDI protrusion-retraction pacemaker in migrating cells. Nature Cell Biol.13, 661–668 (2011). Activation of PKA at the leading edge of cells coordinates protrusion and retraction through a mechanism involving PKA-mediated phosphorylation of RHOA on Ser188, which promotes RHOA binding to RHOGDI and inhibition of RHOA activity. ArticleCAS Google Scholar
Jaffe, A. B. & Hall, A. Rho GTPases: biochemistry and biology. Annu. Rev. Cell Dev. Biol.21, 247–269 (2005). ArticleCASPubMed Google Scholar
O'Connor, K. L., Nguyen, B. K. & Mercurio, A. M. RhoA function in lamellae formation and migration is regulated by the α6β4 integrin and cAMP metabolism. J. Cell Biol.148, 253–258 (2000). ArticleCASPubMedPubMed Central Google Scholar
Ishizaki, H. et al. Defective chemokine-directed lymphocyte migration and development in the absence of Rho guanosine diphosphate-dissociation inhibitors α and β. J. Immunol.177, 8512–8521 (2006). ArticleCASPubMed Google Scholar
Moissoglu, K., McRoberts, K. S., Meier, J. A., Theodorescu, D. & Schwartz, M. A. Rho GDP dissociation inhibitor 2 suppresses metastasis via unconventional regulation of RhoGTPases. Cancer Res.69, 2838–2844 (2009). ArticleCASPubMedPubMed Central Google Scholar
Bielek, H., Anselmo, A. & Dermardirossian, C. Morphological and proliferative abnormalities in renal mesangial cells lacking RhoGDI. Cell Signal.21, 1974–1983 (2009). ArticleCASPubMedPubMed Central Google Scholar
Gorovoy, M. et al. RhoGDI-1 modulation of the activity of monomeric RhoGTPase RhoA regulates endothelial barrier function in mouse lungs. Circ. Res.101, 50–58 (2007). ArticleCASPubMed Google Scholar
Harding, M. A. & Theodorescu, D. RhoGDI signaling provides targets for cancer therapy. Eur. J. Cancer46, 1252–1259 (2010). ArticleCASPubMed Google Scholar
Jones, M. B. et al. Proteomic analysis and identification of new biomarkers and therapeutic targets for invasive ovarian cancer. Proteomics2, 76–84 (2002). ArticleCASPubMed Google Scholar
Zhao, L., Wang, H., Li, J., Liu, Y. & Ding, Y. Overexpression of Rho GDP-dissociation inhibitor α is associated with tumor progression and poor prognosis of colorectal cancer. J. Proteome Res.7, 3994–4003 (2008). ArticleCASPubMed Google Scholar
Zhao, L., Wang, H., Sun, X. & Ding, Y. Comparative proteomic analysis identifies proteins associated with the development and progression of colorectal carcinoma. FEBS J.277, 4195–4204 (2010). ArticleCASPubMed Google Scholar
Forget, M.-A. et al. The expression of rho proteins decreases with human brain tumor progression: potential tumor markers. Clin. Exp. Metastasis19, 9–15 (2002). ArticleCASPubMed Google Scholar
Fritz, G., Lang, P. & Just, I. Tissue-specific variations in the expression and regulation of the small GTP-binding protein Rho. Biochim. Biophys. Acta1222, 331–338 (1994). ArticleCASPubMed Google Scholar
Jiang, W. G. et al. Prognostic value of rho GTPases and rho guanine nucleotide dissociation inhibitors in human breast cancers. Clin. Cancer Res.9, 6432–6440 (2003). CASPubMed Google Scholar
Ding, J. et al. Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA. Nature Cell Biol.12, 390–399 (2010). During hepatocellular carcinoma progression and tumour cell invasion, RHOGDI1 expression is downregulated by miR-151, which is encoded within an intron of the gene encoding FAK. ArticleCASPubMed Google Scholar
Harding, M. A. & Theodorescu, D. RhoGDI2: a new metastasis suppressor gene: discovery and clinical translation. Urol. Oncol.25, 401–406 (2007). ArticleCASPubMed Google Scholar
Abiatari, I. et al. Consensus transcriptome signature of perineural invasion in pancreatic carcinoma. Mol. Cancer Ther.8, 1494–1504 (2009). ArticleCASPubMed Google Scholar
Koide, N. et al. Establishment of perineural invasion models and analysis of gene expression revealed an invariant chain (CD74) as a possible molecule involved in perineural invasion in pancreatic cancer. Clin. Cancer Res.12, 2419–2426 (2006). ArticleCASPubMed Google Scholar
Seraj, M. J., Harding, M. A., Gildea, J. J., Welch, D. R. & Theodorescu, D. The relationship of BRMS1 and RhoGDI2 gene expression to metastatic potential in lineage related human bladder cancer cell lines. Clin. Exp. Metastasis18, 519–525 (2000). ArticleCASPubMed Google Scholar
Theodorescu, D. et al. Reduced expression of metastasis suppressor RhoGDI2 is associated with decreased survival for patients with bladder cancer. Clin. Cancer Res.10, 3800–3806 (2004). ArticleCASPubMed Google Scholar
Ma, L. et al. Loss of expression of LyGDI (ARHGDIB), a rho GDP-dissociation inhibitor, in Hodgkin lymphoma. Br. J. Haematol.139, 217–223 (2007). ArticleCASPubMed Google Scholar
Hu, L. D., Zou, H. F., Zhan, S. X. & Cao, K. M. Biphasic expression of RhoGDI2 in the progression of breast cancer and its negative relation with lymph node metastasis. Oncol. Rep.17, 1383–1389 (2007). PubMed Google Scholar
Wang, Y. et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet365, 671–679 (2005). ArticleCASPubMed Google Scholar
Habets, G. G. et al. Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP–GTP exchangers for Rho-like proteins. Cell77, 537–549 (1994). ArticleCASPubMed Google Scholar
Hordijk, P. L. et al. Inhibition of invasion of epithelial cells by Tiam1–Rac signaling. Science278, 1464–1466 (1997). ArticleCASPubMed Google Scholar
Mehta, D., Rahman, A. & Malik, A. B. Protein kinase C-α signals rho-guanine nucleotide dissociation inhibitor phosphorylation and rho activation and regulates the endothelial cell barrier function. J. Biol. Chem.276, 22614–22620 (2001). ArticleCASPubMed Google Scholar
Knezevic, N. et al. GDI-1 phosphorylation switch at serine 96 induces RhoA activation and increased endothelial permeability. Mol. Cell. Biol.27, 6323–6333 (2007). ArticleCASPubMedPubMed Central Google Scholar
Qiao, J. et al. Phosphorylation of GTP dissociation inhibitor by PKA negatively regulates RhoA. Am. J. Physiol. Cell Physiol.295, C1161–C1168 (2008). ArticleCASPubMedPubMed Central Google Scholar
Guerrera, I. C., Keep, N. H. & Godovac-Zimmermann, J. Proteomics study reveals cross-talk between Rho guanidine nucleotide dissociation inhibitor 1 post-translational modifications in epidermal growth factor stimulated fibroblasts. J. Proteome Res.6, 2623–2630 (2007). ArticleCASPubMed Google Scholar
Kuribayashi, K. et al. Essential role of protein kinase C ζ in transducing a motility signal induced by superoxide and a chemotactic peptide, fMLP. J. Cell Biol.176, 1049–1060 (2007). ArticleCASPubMedPubMed Central Google Scholar
DerMardirossian, C., Rocklin, G., Seo, J.-Y. & Bokoch, G. M. Phosphorylation of RhoGDI by Src regulates Rho GTPase binding and cytosol-membrane cycling. Mol. Biol. Cell17, 4760–4768 (2006). ArticleCASPubMedPubMed Central Google Scholar
Wu, Y. et al. Src phosphorylation of RhoGDI2 regulates its metastasis suppressor function. Proc. Natl Acad. Sci. USA106, 5807–5812 (2009). ArticleCASPubMedPubMed Central Google Scholar
Fei, F. et al. The Fer tyrosine kinase regulates interactions of Rho GDP-dissociation inhibitor α with the small GTPase Rac. BMC Biochem.11, 48 (2010). ArticleCASPubMedPubMed Central Google Scholar
Sauzeau, V., Rolli-Derkinderen, M., Marionneau, C., Loirand, G. & Pacaud, P. RhoA expression is controlled by nitric oxide through cGMP-dependent protein kinase activation. J. Biol. Chem.278, 9472–9480 (2003). ArticleCASPubMed Google Scholar
Lang, P. et al. Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes. EMBO J.15, 510–519 (1996). ArticleCASPubMedPubMed Central Google Scholar
Dong, J. M., Leung, T., Manser, E. & Lim, L. cAMP-induced morphological changes are counteracted by the activated RhoA small GTPase and the Rho kinase ROKα. J. Biol. Chem.273, 22554–22562 (1998). ArticleCASPubMed Google Scholar
Tamma, G. et al. cAMP-induced AQP2 translocation is associated with RhoA inhibition through RhoA phosphorylation and interaction with RhoGDI. J. Cell Sci.116, 1519–1525 (2003). ArticleCASPubMed Google Scholar
Ellerbroek, S. M., Wennerberg, K. & Burridge, K. Serine phosphorylation negatively regulates RhoA in vivo. J. Biol. Chem.278, 19023–19031 (2003). ArticleCASPubMed Google Scholar
Guilluy, C. et al. Ste20-related kinase SLK phosphorylates Ser188 of RhoA to induce vasodilation in response to angiotensin II type 2 receptor activation. Circ. Res.102, 1265–1274 (2008). ArticleCASPubMed Google Scholar
Forget, M. A., Desrosiers, R. R., Gingras, D. & Beliveau, R. Phosphorylation states of Cdc42 and RhoA regulate their interactions with Rho GDP dissociation inhibitor and their extraction from biological membranes. Biochem. J.361, 243–254 (2002). ArticleCASPubMedPubMed Central Google Scholar
Tu, S., Wu, W. J., Wang, J. & Cerione, R. A. Epidermal growth factor-dependent regulation of Cdc42 is mediated by the Src tyrosine kinase. J. Biol. Chem.278, 49293–49300 (2003). ArticleCASPubMed Google Scholar
Schoentaube, J., Olling, A., Tatge, H., Just, I. & Gerhard, R. Serine-71 phosphorylation of Rac1/Cdc42 diminishes the pathogenic effect of Clostridium difficile toxin A. Cell. Microbiol.11, 1816–1826 (2009). ArticleCASPubMed Google Scholar
Kwon, T., Kwon, D. Y., Chun, J., Kim, J. H. & Kang, S. S. Akt protein kinase inhibits Rac1-GTP binding through phosphorylation at serine 71 of Rac1. J. Biol. Chem.275, 423–428 (2000). ArticleCASPubMed Google Scholar