GPCRs that Rhoar the Guanine nucleotide exchange factors

References

• Trepat X, Chen Z, Jacobson K. Cell migration. Compr Physiol. 2012;2(4):2369–2392.
   PubMed Web of Science ®Google Scholar
• Zegers MM, Friedl P. Rho GTPases in collective cell migration. Small GTPases 2014; 5:e983869.
   Google Scholar
• Paoletti S, Petkovic V, Sebastiani S, et al. A rich chemokine environment strongly enhances leukocyte migration and activities. Blood. 2005;105(9):3405–3412.
   PubMed Web of Science ®Google Scholar
• Peplow PV, Chatterjee MP. A review of the influence of growth factors and cytokines in in vitro human keratinocyte migration. Cytokine. 2013;62(1):1–21.
   PubMed Web of Science ®Google Scholar
• Coombs VA, Nissen BK, Marks R, et al. The influence of temperature on epidermal cell migration in vitro. Br J Exp Pathol. 1973;54(6): 673–677. PMID: 4798773.
   PubMedGoogle Scholar
• Su C, Zhang B, Liu W, et al. High extracellular pressure promotes gastric cancer cell adhesion, invasion, migration and suppresses gastric cancer cell differentiation. Oncol Rep. 2016;36(2):1048–1054.
   PubMed Web of Science ®Google Scholar
• Ridley AJ, Schwartz MA, Burridge K, et al. Cell migration: integrating signals from front to back. Science. 2003;302(5651):1704–1709.
   PubMed Web of Science ®Google Scholar
• Martin K, Reimann A, Fritz RD, et al. Spatio-temporal co-ordination of RhoA, Rac1 and Cdc42 activation during prototypical edge protrusion and retraction dynamics. Sci Rep. 2016;6(1):1–14.
   PubMedGoogle Scholar
• Ridley AJ, Hall A. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell. 1992;70(3):389–399.
   PubMed Web of Science ®Google Scholar
• Nobes CD, Hall A. Rho 1. nobes CD, hall A. Rho GTPases control polarity, protrusion, and adhesion during cell movement. J Cell Biol. 1999;144(6):1235–1244.
   PubMed Web of Science ®Google Scholar
• Nobes CD, Rho HA. Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell. 1995;81(1):53–62.
   PubMed Web of Science ®Google Scholar
• Van Leeuwen FN, Olivo C, Grivell S, et al. Rac activation by lysophosphatidic acid LPA1 receptors through the guanine nucleotide exchange factor Tiam1. J Biol Chem. 2003;278(1):400–406.
   PubMed Web of Science ®Google Scholar
• Manser E, Loo TH, Koh CG, et al. PAK kinases are directly coupled to the PIX family of nucleotide exchange factors. Mol Cell. 1998;1(2):183–192.
   PubMed Web of Science ®Google Scholar
• Bos JL, Rehmann H, Wittinghofer A. GEFs and GAPs: critical elements in the control of small G proteins. Cell. 2007;129(5):865–877.
   PubMed Web of Science ®Google Scholar
• Cho HJ, Kim BY, Baek KE, et al. Regulation of Rho GTPases by RhoGDIs in human cancers. Cells. 2019;8(9):1–12.
   Web of Science ®Google Scholar
• Buchsbaum RJ. Rho activation at a glance. J Cell Sci. 2007;120(7):1149–1152.
   PubMed Web of Science ®Google Scholar
• Dovas A, Couchman JR. RhoGDI: multiple functions in the regulation of Rho family GTPase activities. Biochem J. 2005;390(1):1–9.
   PubMedGoogle Scholar
• Goicoechea SM, Awadia S, Garcia-Mata R. I’m coming to GEF you: regulation of RhoGEFs during cell migration. Cell Adhes Migr. 2014;8(6):535–549.
   PubMed Web of Science ®Google Scholar
• Zheng Y, Quilliam LA. Activation of the Ras superfamily of small GTPases.Workshop on exchange factors. EMBO Rep. 2003;4(5):463–468.
   PubMedGoogle Scholar
• Hartmann S, Ridley AJ, Lutz S. The function of rho-associated kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease. Front Pharmacol. 2015;6:276.
   PubMed Web of Science ®Google Scholar
• Hilger D, Masureel M, Kobilka BK. Structure and dynamics of GPCR signaling complexes. Nat Struct Mol Biol. 2018;25(1):4–12.
   PubMed Web of Science ®Google Scholar
• Heng BC, Aubel D, Fussenegger M. An overview of the diverse roles of G-protein coupled receptors (GPCRs) in the pathophysiology of various human diseases. Biotechnol Adv. 2013;31:1676–1694.
   PubMed Web of Science ®Google Scholar
• Du Z, Lovly CM. Mechanisms of receptor tyrosine kinase activation in cancer. Mol Cancer. 2018;17:1–13.
   PubMed Web of Science ®Google Scholar
• Hamidi H, Ivaska J. Every step of the way: integrins in cancer progression and metastasis. Nat Rev Cancer. 2018;18(1):1–16.
   PubMedGoogle Scholar
• Cotton M, Claing A. G protein-coupled receptors stimulation and the control of cell migration. Cell Signal. 2009;21(7):1045–1053.
   PubMed Web of Science ®Google Scholar
• Rossman KL, Der CJ, Sondek J. GEF means go: turning on Rho GTPases with guanine nucleotide-exchange factors. Nature Reviews Molecular Cell Biology. 2005;6(2):167–180.
   PubMed Web of Science ®Google Scholar
• Viaud J, Lagarrigue F, Ramel D, et al. Phosphatidylinositol 5-phosphate regulates invasion through binding and activation of Tiam1. Nat Commun. 2014;5(1):1–17.
   Google Scholar
• Baumeister MA, Martinu L, Rossman KL, et al. Loss of phosphatidylinositol 3-phosphate binding by the C-terminal Tiam-1 pleckstrin homology domain prevents in vivo Rac1 activation without affecting membrane targeting. J Biol Chem. 2003;278(13):11457–11464.
   PubMed Web of Science ®Google Scholar
• Schmidt A, Hall A. Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev. 2002;16(13):1587–1609.
   PubMed Web of Science ®Google Scholar
• Consonni SV, Brouwer PM, Van Slobbe ES, et al. The PDZ domain of the guanine nucleotide exchange factor PDZGEF directs binding to phosphatidic acid during brush border formation. PLoS One. 2014;9(5):e98253.
   PubMed Web of Science ®Google Scholar
• Fukuharaa S, Chikumi H, Silvio Gutkind J. RGS-containing RhoGEFs: the missing link between transforming G proteins and Rho? Oncogene. 2001;20(13):1661–1668.
   PubMed Web of Science ®Google Scholar
• Xu Z, Gakhar L, Bain FE, et al. The Tiam1 guanine nucleotide exchange factor is autoinhibited by its pleckstrin homology coiled-coil extension domain. J Biol Chem. 2017;292(43):17777–17793.
   PubMed Web of Science ®Google Scholar
• Premkumar L, Bobkov AA, Patel M, et al. Structural basis of membrane targeting by the Dock180 family of Rho family guanine exchange factors (Rho-GEFs). J Biol Chem. 2010;285(17):13211–13222.
   PubMed Web of Science ®Google Scholar
• Brugnera E, Haney L, Grimsley C, et al. Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. Nat Cell Biol. 2002;4(8):574–582.
   PubMed Web of Science ®Google Scholar
• Kulkarni K, Yang J, Zhang Z, et al. Multiple factors confer specific Cdc42 and Rac protein activation by dedicator of cytokinesis (DOCK) nucleotide exchange factors. J Biol Chem. 2011;286(28):25341–25351.
   PubMed Web of Science ®Google Scholar
• Chang L, Yang J, Jo CH, et al. Structure of the DOCK2−ELMO1 complex provides insights into regulation of the auto-inhibited state. Nat Commun. 2020;11(1):1–17.
   PubMed Web of Science ®Google Scholar
• Lu M, Kinchen JM, Rossman KL, et al. A steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs. Curr Biol. 2005;15(4):371–377.
   PubMed Web of Science ®Google Scholar
• Chen Z, Guo L, Hadas J, et al. Activation of p115-RhoGEF requires direct association of Gα13 and the Dbl homology domain. J Biol Chem. 2012;287(30):25490–25500.
   PubMed Web of Science ®Google Scholar
• Patel M, Karginov AV. Phosphorylation-mediated regulation of GEFs for RhoA. Cell Adhes Migr. 2014;8(1):11–18.
   PubMed Web of Science ®Google Scholar
• Booden MA, Siderovski DP, Der CJ. Leukemia-associated Rho Guanine nucleotide exchange factor promotes Gαq-coupled activation of RhoA. Mol Cell Biol. 2002;22(12):4053–4061.
   PubMed Web of Science ®Google Scholar
• Martin JW, Cavagnini KS, Brawley DN, et al. A Gα12-specific binding domain in AKAP-Lbc and p114RhoGEF. J Mol Signal. 2016;11:1–17.
   PubMedGoogle Scholar
• Bartolomé RA, Molina-Ortiz I, Samaniego R, et al. Activation of Vav/Rho GTPase signaling by CXCL12 controls membrane-type matrix metalloproteinase-dependent melanoma cell invasion. Cancer Res. 2006;66(1):248–258.
   PubMed Web of Science ®Google Scholar
• Yamada T, Ohoka Y, Kogo M, et al. Physical and functional interactions of the lysophosphatidic acid receptors with PDZ domain-containing Rho guanine nucleotide exchange factors (RhoGEFs). J Biol Chem. 2005;280(19):19358–19363.
   PubMed Web of Science ®Google Scholar
• Kourlas PJ, Strout MP, Becknell B, et al. Identification of a gene at 11q23 encoding a guanine nucleotide exchange factor: evidence for its fusion with MLL in acute myeloid leukemia. Proc Natl Acad Sci U S A. 2000;97(5):2145–2150.
   PubMed Web of Science ®Google Scholar
• Medlin MD, Staus DP, Dubash AD, et al. Sphingosine 1-phosphate receptor 2 signals through leukemia-associated RhoGEF (LARG), to promote smooth muscle cell differentiation. Arterioscler Thromb Vasc Biol. 2010;30(9):1779–1786.
   PubMed Web of Science ®Google Scholar
• Wang Q, Liu M, Kozasa T, et al. Thrombin and lysophosphatidic acid receptors utilize distinct rhoGEFs in prostate cancer cells. J Biol Chem. 2004;279(28):28831–28834.
   PubMed Web of Science ®Google Scholar
• Goulimari P, Knieling H, Engel U, et al. LARG and mDia1 Link Gα 12/13 to Cell Polarity and Microtubule Dynamics. Mol Biol Cell. 2008;19(1):30–40.
   PubMed Web of Science ®Google Scholar
• Patel M, Kawano T, Suzuki N, et al. Gα13/PDZ-RhoGEF/RhoA signaling is essential for gastrin- releasing peptide receptor – mediated colon cancer cell migration. Molecular Pharmacology. 2014;86(3):252–262.
   PubMed Web of Science ®Google Scholar
• Struckhoff AP, Rana MK, Kher SS, et al. PDZ-RhoGEF is essential for CXCR4-driven breast tumor cell motility through spatial regulation of RhoA. J Cell Sci. 2013;126(19):4514–4526.
   PubMed Web of Science ®Google Scholar
• Mathew D, Kremer KN, Torres RM. ARHGEF1 deficiency reveals Gα13-associated GPCRs are critical regulators of human lymphocyte function. J Clin Invest. 2019;129(3):965–968.
   PubMed Web of Science ®Google Scholar
• Castillo-Kauil A, García-Jiménez I, Cervantes-Villagrana RD, et al. Gαsdirectly drives PDZ-RhoGEF signaling to Cdc42. J Biol Chem. 2020;295(50):16920–16928.
   PubMed Web of Science ®Google Scholar
• Slepak VZ, Pronin A. A Gs-RhoGEF interaction: an old G protein finds a new job. J Biol Chem. 2020;295(50):16929–16930.
   PubMed Web of Science ®Google Scholar
• Fukuhara S, Murga C, Zohar M, et al. A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho. J Biol Chem. 1999;274(9):5868–5879.
   PubMed Web of Science ®Google Scholar
• Scarlett KA, White ESZ, Coke CJ, et al. Agonist-induced CXCR4 and CB2 heterodimerization inhibits Gα13/RhoA-mediated migration. Mol Cancer Res. 2018;16(4):728–739.
   PubMed Web of Science ®Google Scholar
• Ma X, Zhao Y, Daaka Y, et al. Acute activation of β2-adrenergic receptor regulates focal adhesions through βArrestin2- and p115RhoGEF protein-mediated activation of RhoA. J Biol Chem. 2012;287(23):18925–18936.
   PubMed Web of Science ®Google Scholar
• Chen Z, Guo L, Sprang SR, et al. Modulation of a GEF switch: autoinhibition of the intrinsic guanine nucleotide exchange activity of p115-RhoGEF. Protein Sci. 2011;20:(1):107–117.
   PubMed Web of Science ®Google Scholar
• Appert-Collin A, Cotecchia S, Nenniger-Tosato M, et al. The A-kinase anchoring protein (AKAP)-Lbc-signaling complex mediates α1 adrenergic receptor-induced cardiomyocyte hypertrophy. Proc Natl Acad Sci U S A. 2007;104(24):10140–10145.
   PubMed Web of Science ®Google Scholar
• Turton KB, Wilkerson EM, Hebert AS, et al. Expression of novel “LOCGEF” isoforms of ARHGEF18 in eosinophils. J Leukoc Biol. 2018;104(1):135–145.
   PubMed Web of Science ®Google Scholar
• Cervantes-Villagrana RD, Color-Aparicio VM, Reyes-Cruz G, et al. Protumoral bone marrow-derived cells migrate via Gβγ-dependent signaling pathways and exhibit a complex repertoire of RhoGEFs. J Cell Commun Signal. 2019;13(2):179–191.
   PubMed Web of Science ®Google Scholar
• Jaiswal M, Dvorsky R, Ahmadian MR. Deciphering the molecular and functional basis of Dbl family proteins: a novel systematic approach toward classification of selective activation of the Rho family proteins. J Biol Chem. 2013;288(6):4486–4500.
   PubMed Web of Science ®Google Scholar
• Welch HCE Regulation and function of P-Rex family Rac-GEFs. 2015; 6:49–70.
   Google Scholar
• Niggli V. Signaling to migration in neutrophils: importance of localized pathways. Int J Biochem Cell Biol. 2003;35(12):1616–1638.
   Web of Science ®Google Scholar
• Mazaki Y, Hashimoto S, Tsujimura T, et al. Neutrophil direction sensing and superoxide production linked by the GTPase-activating protein GIT2. Nat Immunol. 2006;7(7):724–731.
   PubMed Web of Science ®Google Scholar
• Premont RT, Perry SJ, Schmalzigaug R, et al. The GIT/PIX complex: an oligomeric assembly of GIT family ARF GTPase-activating proteins and PIX family Rac1/Cdc42 guanine nucleotide exchange factors. Cell Signal. 2004;16(9):1001–1011.
   PubMed Web of Science ®Google Scholar
• Bustelo XR. The VAV family of signal transduction molecules. Crit. Rev. Oncog. 1996;7(1–2):65–88.
   PubMed Web of Science ®Google Scholar
• Razidlo GL, Schroeder B, Chen J, et al. Vav1 as a central regulator of invadopodia assembly. Curr Biol. 2014;24(1):86–93.
   PubMed Web of Science ®Google Scholar
• Fujikawa K, Miletic AV, Alt FW, et al. Vav1/2/3-null Mice Define an Essential Role for Vav Family Proteins in Lymphocyte Development and Activation but a Differential Requirement in MAPK Signaling in T and B Cells. J Exp Med. 2003;198(10):1595–1608.
   PubMed Web of Science ®Google Scholar
• Shepherd TR, Hard RL, Murray AM, et al. Distinct ligand specificity of the Tiam1 and Tiam2 PDZ domains. Biochemistry. 2011;50(8):1296–1308.
   PubMed Web of Science ®Google Scholar
• Wang Y, Xu X, Pan M, et al. ELMO1 directly interacts with Gβγ subunit to transduce GPCR signaling to Rac1 activation in chemotaxis. J Cancer. 2016;7(8):973–983.
   PubMed Web of Science ®Google Scholar
• Kunimura K, Uruno T, Fukui Y. DOCK family proteins: key players in immune surveillance mechanisms. Int Immunol. 2020;32(1):5–15.
   PubMed Web of Science ®Google Scholar
• Fukui Y, Hashimoto O, Sanui T, et al. Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration. Nature. 2001;412(6849):826–831.
   PubMed Web of Science ®Google Scholar
• Diviani D, Soderling J, Scott JD. AKAP-Lbc anchors protein kinase a and nucleates Gα12-selective Rho-mediated stress fiber formation. J Biol Chem. 2001;276(47):44247–44257.
   PubMed Web of Science ®Google Scholar
• Cavin S, Maric D, Diviani D. A-kinase anchoring protein-Lbc promotes pro-fibrotic signaling in cardiac fibroblasts. Biochim Biophys Acta Mol Cell Res. 2014;1843(2):335–345.
   PubMed Web of Science ®Google Scholar
• Aittaleb M, Boguth CA, Tesmer JJG. Structure and function of heterotrimeric G protein-regulated Rho guanine nucleotide exchange factors. Mol Pharmacol. 2010;77(2):111–125.
   PubMed Web of Science ®Google Scholar
• O’Connor KL, Chen M, Towers LN. Integrin α6β4 cooperates with LPA signaling to stimulate Rac through AKAP-LBc-mediated RhoA activation. Am J Physiol Cell Physiol. 2012;302:2–11.
   Web of Science ®Google Scholar
• Paulucci-Holthauzen AA, Vergara LA, Bellot LJ, et al. Spatial distribution of protein kinase A activity during cell migration is mediated by A-kinase anchoring protein AKAP Lbc. J Biol Chem. 2009;284(9):5956–5967.
   PubMed Web of Science ®Google Scholar
• Blomquist A, Schwörer G, Schablowski H, et al. Identification and characterization of a novel Rho-specific guanine nucleotide exchange factor. Biochem J. 2000;352(2):319–325.
   PubMedGoogle Scholar
• Niu J, Profirovic J, Pan H, et al. g protein βγ subunits stimulate p114rhogef, a guanine nucleotide exchange factor for RhoA and Rac1: regulation of cell shape and reactive oxygen species production. Circ Res. 2003;93(9):848–856.
   PubMed Web of Science ®Google Scholar
• Terry SJ, Elbediwy A, Zihni C, et al. Stimulation of cortical myosin phosphorylation by p114RhoGEF drives cell migration and tumor cell invasion. PLoS One. 2012;7(11):e50188.
   PubMed Web of Science ®Google Scholar
• Philippe JM, Lellouch AC, Lecuit T, Garcia De Las Bayonas A. Distinct RhoGEFs activate apical and junctional contractility under control of G Proteins during Epithelial Morphogenesis. Curr Biol. 2019;29(20):3370–3385.e7. .
   PubMed Web of Science ®Google Scholar
• Marivin A, Morozova V, Walawalkar I, et al. GPCR-independent activation of G proteins promotes apical cell constriction in vivo. J Cell Biol. 2019;218(5):1743–1763.
   PubMed Web of Science ®Google Scholar
• Souchet M, Portales-Casamar E, Mazurais D, et al. Human p63RhoGEF, a novel RhoA-specific guanine nucleotide exchange factor, is localized in cardiac sarcomere. J Cell Sci. 2002;115(Pt 3):629–640. PubMed 11861769.
   PubMed Web of Science ®Google Scholar
• Lutz S, Freichel-Blomquist A, Yang Y, et al. The guanine nucleotide exchange factor p63RhoGEF, a specific link between Gq/11-coupled receptor signaling and RhoA. J Biol Chem. 2005;280(12):11134–11139.
   PubMed Web of Science ®Google Scholar
• Lutz S, Shankaranarayanan A, Coco C, et al. Structure of Gαq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs. Science. 2007;318(5858):1923–1927. (80-).
   PubMed Web of Science ®Google Scholar
• Rojas RJ, Yohe ME, Gershburg S, et al. Gαq directly activates p63RhoGEF and trio via a conserved extension of the Dbl homology-associated pleckstrin homology domain. J Biol Chem. 2007;282(40):29201–29210.
   PubMed Web of Science ®Google Scholar
• Guo X, Stafford LJ, Bryan B, et al. A Rac/ Cdc42-specific exchange factor, GEFT, induces cell proliferation, transformation, and migration. J Biol Chem. 2003;278(15):13207–13215.
   PubMed Web of Science ®Google Scholar
• Kruse K, Lee QS, Sun Y, et al. N-cadherin signaling via Trio assembles adherens junctions to restrict endothelial permeability. J Cell Biol. 2019;218(1):299–316.
   PubMed Web of Science ®Google Scholar
• Cervantes-Villagrana RD, Adame-García SR, García-Jiménez I, et al. Gβγ signaling to the chemotactic effector P-REX1 and mammalian cell migration is directly regulated by Gαq and Gα13 proteins. J Biol Chem. 2019;294(2):531–546.
   PubMed Web of Science ®Google Scholar
• Sosa MS, Lopez-Haber C, Yang C, et al. Identification of the Rac-GEF P-Rex1 as an Essential Mediator of ErbB signaling in breast cancer. Mol Cell. 2010;40:(6):877–892.
   PubMed Web of Science ®Google Scholar
• Carretero-Ortega J, Walsh CT, Hernández-García R, et al. Phosphatidylinositol 3,4,5-triphosphate-dependent rac exchanger 1 (P-Rex-1), a guanine nucleotide exchange factor for rac, mediates angiogenic responses to stromal cell-derived factor-1/chemokine stromal cell derived factor-1 (SDF-1/CXCL-12) linked to rac. Mol Pharmacol. 2010;77(3):435–442.
   PubMed Web of Science ®Google Scholar
• Cash JN, Urata S, Li S, et al. Cryo-electron microscopy structure and analysis of the P-Rex1-Gβγ signaling scaffold. Sci Adv. 2019;5(10):eaax8855.
   PubMed Web of Science ®Google Scholar
• Damoulakis G, Gambardella L, Rossman KL, et al. P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils. J Cell Sci. 2014;127(11):2589–2600.
   PubMed Web of Science ®Google Scholar
• Koh CG, Manser E, Zhao ZS, et al. β1PIX, the PAK-interacting exchange factor, requires localization via a coiled-coil region to promote microvillus-like structures and membrane ruffles. J Cell Sci. 2001;114(Pt 23): 4239–4251. PubMed:11739656.
   PubMed Web of Science ®Google Scholar
• Ward JD, Ha JH, Jayaraman M, et al. LPA-mediated migration of ovarian cancer cells involves translocalization of Gαi2 to invadopodia and association with Src and β-pix. Cancer Lett. 2015;356(2):382–391.
   PubMed Web of Science ®Google Scholar
• Feng Q, Baird D, Yoo S, et al. Phosphorylation of the cool-1/β-pix protein serves as a regulatory signal for the migration and invasive activity of Src-transformed cells. J Biol Chem. 2010;285(24):18806–18816.
   PubMed Web of Science ®Google Scholar
• Feng Q, Baird D, Peng X, et al. Cool-1 functions as an essential regulatory node for EGF receptor and Src-mediated cell growth. Nat Cell Biol. 2006;8(9):945–956.
   PubMed Web of Science ®Google Scholar
• Mayhew MW, Jeffery ED, Sherman NE, et al. Identification of phosphorylation sites in βPIX and PAK1. J Cell Sci. 2007;120(22):3911–3918.
   PubMed Web of Science ®Google Scholar
• Chahdi A, Miller B, Sorokin A. Endothelin 1 induces β1Pix translocation and Cdc42 activation via protein kinase A-dependent pathway. J Biol Chem. 2005;280(1):578–584.
   PubMed Web of Science ®Google Scholar
• Chahdi A, Sorokin A. The role of β1Pix/caveolin-1 interaction in endothelin signaling through Gα subunits. Biochem Biophys Res Commun. 2010;391(3):1330–1335.
   PubMed Web of Science ®Google Scholar
• Frank SR, Hansen SH. The PIX-GIT complex: a G protein signaling cassette in control of cell shape. Semin. 2008;19:234–244. Cell Dev. Biol.
   Google Scholar
• Zhou W, Li X, Premont RT. Expanding functions of GIT Arf GTPase-activating proteins, PIX Rho guanine nucleotide exchange factors and GIT-PIX complexes. J Cell Sci. 2016;129(10):1963–1974.
   PubMed Web of Science ®Google Scholar
• Feng Q, Albeck JG, Cerione RA, et al. Regulation of the Cool/Pix proteins. Key binding partners of the Cdc42/Rac targets, the p21-activated kinases. J Biol Chem. 2002;277(7):5644–5650.
   PubMed Web of Science ®Google Scholar
• Yoshii S, Tanaka M, Otsuki Y, et al. αPIX nucleotide exchange factor is activated by interaction with phosphatidylinositol 3-kinase. Oncogene. 1999;18(41):5680–5690.
   PubMed Web of Science ®Google Scholar
• Lyda JK, Tan ZL, Rajah A, et al. Rac activation is key to cell motility and directionality: an experimental and modelling investigation. Comput Struct Biotechnol J. 2019;17:1436–1452.
   PubMed Web of Science ®Google Scholar
• Lawson CD, Donald S, Anderson KE, et al., Welch HCE. P-Rex1 and Vav1 cooperate in the regulation of Formyl-Methionyl-Leucyl-Phenylalanine–Dependent Neutrophil Responses. J Immunol. 2011;186(3):1467–1476. .
   PubMed Web of Science ®Google Scholar
• Heo J, Thapar R, Campbell SL. Recognition and activation of Rho GTPases by Vav1 and Vav2 Guanine nucleotide exchange factors †. Biochemistry. 2005;17(17):6573–6585.
   Google Scholar
• Bustelo XR. Regulatory and signaling properties of the Vav Family. Mol Cell Biol. 2000;20(5):1461–1477.
   PubMed Web of Science ®Google Scholar
• Vila‐Coro AJ, Rodríguez‐Frade JM, De Ana AM, et al. The chemokine SDF‐lα triggers CXCR4 receptor dimerization and activates the JAK/STAT pathway. Faseb J. 1999;13(13):1699–1710.
   PubMed Web of Science ®Google Scholar
• Fumagalli L, Zhang H, Baruzzi A, et al. The Src family Kinases Hck and Fgr regulate Neutrophil responses to N Formyl-Methionyl-Leucyl-Phenylalanine. J Immunol. 2007;178(6):3874–3885.
   PubMed Web of Science ®Google Scholar
• Aghazadeh B, Lowry WE, Huang XY, et al. Structural basis for relief of autoinhibition of the Dbl homology domain of proto-oncogene Vav by tyrosine phosphorylation. Cell. 2000;102(5):625–633.
   PubMed Web of Science ®Google Scholar
• Fleming IN, Elliott CM, Buchanan FG, et al. Ca2+/Calmodulin-dependent Protein Kinase II regulates Tiam1 by reversible protein Phosphorylation. Biochemistry. 1999;274:12753–12758.
   Google Scholar
• Miyamoto Y, Yamauchi J, Tanoue A, et al. TrkB binds and tyrosine-phosphorylates Tiam1, leading to activation of Rac1 and induction of changes in cellular morphology. Proc Natl Acad Sci U S A. 2006;103:10444–10449.
   PubMed Web of Science ®Google Scholar
• Minard ME, Kim LS, Price JE, et al. The role of the guanine nucleotide exchange factor Tiam1 in cellular migration, invasion, adhesion and tumor progression. Breast Cancer Res Treat. 2004;84(1):21–32.
   PubMed Web of Science ®Google Scholar
• Wang S, Watanabe T, Matsuzawa K, et al. Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration. J Cell Biol. 2012;199(2):331–345.
   PubMed Web of Science ®Google Scholar
• Mertens AEE, Pegtel DM, Collard JG. Tiam1 takes PARt in cell polarity. Trends Cell Biol. 2006;16(6):308–316.
   PubMed Web of Science ®Google Scholar
• Fleming IN, Gray A, Downes CP. Regulation of the Rac1-specific exchange factor Tiam1 involves both phosphoinositide 3-kinase-dependent and -independent components. Biochem J. 2000;351(1):173–182.
   PubMedGoogle Scholar
• Hoshino M, Sone M, Fukata M, et al. Identification of the stef gene that encodes a novel guanine nucleotide exchange factor specific for Rac1. J Biol Chem. 1999;274(25):17837–17844.
   PubMed Web of Science ®Google Scholar
• Goto A, Hoshino M, Matsuda M, et al. Phosphorylation of STEF/Tiam2 by protein kinase A is critical for Rac1 activation and neurite outgrowth in dibutyryl cAMP-treated PC12D cells. Mol Biol Cell. 2011;22(10):1780–1790.
   PubMed Web of Science ®Google Scholar
• Emami-Nemini A, Gohla A, Urlaub H, et al. The guanine nucleotide exchange factor Vav2 is a negative regulator of parathyroid hormone Receptor/Gq Signaling. Mol Pharmacol. 2012;82(2):217–225.
   PubMed Web of Science ®Google Scholar
• Schulte G, Wright SC. Frizzleds as GPCRs – more conventional than we thought! trends. 2018;39:828–842. Pharmacol Sci.
   PubMed Web of Science ®Google Scholar
• Gammons MV, Renko M, Johnson CM, et al. Wnt Signalosome Assembly by DEP Domain Swapping of Dishevelled. Mol Cell. 2016;64(1):92–104.
   PubMed Web of Science ®Google Scholar
• Tanegashima K, Zhao H, Dawid IB. WGEF activates Rho in the Wnt-PCP pathway and controls convergent extension in Xenopus gastrulation. Embo J. 2008;27(4):606–617.
   PubMed Web of Science ®Google Scholar
• Li H, Yang L, Fu H, et al. Association between Gαi2 and ELMO1/Dock180 connects chemokine signalling with Rac activation and metastasis. Nat Commun. 2013;4:1–12.
   Web of Science ®Google Scholar
• Ward JD, Dhanasekaran DN. LPA Stimulates the Phosphorylation of p130Cas via Gαi2 in Ovarian Cancer Cells. Genes Cancer. 2012;3(9–10):578–591.
   PubMedGoogle Scholar
• Matsui H, Harada I, Sawada Y. Src, p130Cas, and Mechanotransduction in cancer cells. Genes Cancer. 2012;3(5–6):394–401.
   PubMedGoogle Scholar
• Feng H, Hu B, Liu KW, et al. Activation of Rac1 by Src-dependent phosphorylation of Dock180Y1811 mediates PDGFRα-stimulated glioma tumorigenesis in mice and humans. J Clin Invest. 2011;121(12):4670–4684.
   PubMed Web of Science ®Google Scholar
• Kunisaki Y, Nishikimi A, Tanaka Y, et al. DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis. J Cell Biol. 2006;174(5):647–652.
   PubMed Web of Science ®Google Scholar
• Wang J, Xu L, Shaheen S, et al. Growth of B Cell receptor microclusters is regulated by PIP2 and PIP3 Equilibrium and Dock2 recruitment and activation. Cell Rep. 2017;21(9):2541–2557.
   PubMed Web of Science ®Google Scholar
• Thelen M, Stein JV. How chemokines invite leukocytes to dance. Nat Immunol. 2008;9:(9):953–959.
   PubMed Web of Science ®Google Scholar
• Park D, Tosello-Trampont AC, Elliott MR, et al. BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature. 2007;450(7168):430–434.
   PubMed Web of Science ®Google Scholar
• Weng Z, Situ C, Lin L, et al. Structure of BAI1/ELMO2 complex reveals an action mechanism of adhesion GPCRs via ELMO family scaffolds. Nat Commun. 2019;10(1). 10.1038/s41467-018-07938-9
   Google Scholar
• Afm TI, Yue H, Scavello M, et al. The cAMP-induced G protein subunits dissociation monitored in live Dictyostelium cells by BRET reveals two activation rates, a negative effect of caffeine and potential role of microtubules. Cell Signal. 2018;48:25–37.
   PubMed Web of Science ®Google Scholar
• Islam AFMT, Stepanski BM, Charest PG Studying chemoattractant signal transduction dynamics in Dictyostelium by BRET. In: Methods in Molecular Biology. 2016;1407: 63–77.
   Google Scholar
• Galés C, Rebois RV, Hogue M, et al. Real-time monitoring of receptor and G-protein interactions in living cells. Nat Methods. 2005;3(3):177–184.
   Google Scholar
• Xu X, Brzostowski JA, Jin T. Monitoring dynamic GP CR signaling events using fluorescence microscopy, FRET imaging, and single-molecule imaging. Methods Mol Biol. 2009;571:371–383.
   PubMedGoogle Scholar