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Article

Unravelling the Mechanism of TrkA-Induced Cell Death by Macropinocytosis in Medulloblastoma Daoy Cells

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Pages 2596-2611 | Received 04 May 2016, Accepted 29 Jul 2016, Published online: 17 Mar 2023

REFERENCES

  • Kim JY, Sutton ME, Lu DJ, Cho TA, Goumnerova LC, Goritchenko L, Kaufman JR, Lam KK, Billet AL, Tarbell NJ, Wu J, Allen JC, Stiles CD, Segal RA, Pomeroy SL. 1999. Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas. Cancer Res 59:711–719.
  • Brodeur GM. 2003. Neuroblastoma: biological insights into a clinical enigma. Natue Rev Cancer 3:203–216. http://dx.doi.org/10.1038/nrc1014.
  • Marino S. 2005. Medulloblastoma: developmental mechanisms out of control. Trends Mol Med 11:17–22. http://dx.doi.org/10.1016/j.molmed.2004.11.008.
  • Nakagawara A. 2006. Neural crest development and neuroblastoma: the genetic and biological link. Prog Brain Res 146:231–242.
  • Brodeur GM, Minturn JE, Ho R, Simpson AM, Iyer R, Varela CR, Light JE, Kolla V, Evans AE. 2009. Trk receptor expression and inhibition in neuroblastomas. Clin Cancer Res 15:3244–3250. http://dx.doi.org/10.1158/1078-0432.CCR-08-1815.
  • Gulino A, Arcella A, Giangaspero F. 2008. Pathological and molecular heterogeneity of medulloblastoma. Curr Opin Oncol 20:668–675. http://dx.doi.org/10.1097/CCO.0b013e32831369f4.
  • Harel L, Costa B, Fainzilber M. 2010. On the death Trk. Dev Neurobiol 70:298–303. http://dx.doi.org/10.1002/dneu.20769.
  • Thomaz A, Jaeger M, Buendia M, Bambini-Junior V, Gregianin LJ, Brunetto AL, Brunetto AT, de Farias CB, Roesler R. 2016. BDNF/TrkB signaling as a potential novel target in pediatric brain tumors: anticancer activity of selective TrkB inhibition in medulloblastoma cells. J Mol Neurosci 59:326–333. http://dx.doi.org/10.1007/s12031-015-0689-0.
  • Chou TT, Trojanowski JQ, Lee VM. 2000. A novel apoptotic pathway induced by nerve growth factor-mediated TrkA activation in medulloblastoma. J Biol Chem 275:565–570. http://dx.doi.org/10.1074/jbc.275.1.565.
  • Lavoie JF, LeSauteur L, Kohn J, Wong J, Furtoss O, Thiele CJ, Miller FD, Kaplan DR. 2005. TrkA Induces apoptosis of neuroblastoma cells and does so via a p53-dependent mechanism. J Biol Chem 280:29199–29207. http://dx.doi.org/10.1074/jbc.M502364200.
  • Jung EJ, Kim DR. 2008. Apoptotic cell death in TrkA-overexpressing cells: kinetic regulation of ERK phosphorylation and caspase-7 activation. Mol Cell 26:12–17.
  • Harel L, Costa B, Tcherpakov M, Zapatka M, Oberthuer A, Hansford LM, Vojvodic M, Levy Z, Chen Z-Y, Lee FS, Avigad S, Yaniv I, Shi L, Eils R, Fischer M, Brors B, Kaplan DR, Fainzilber M. 2009. CCM2 mediates death signaling by the TrkA receptor tyrosine kinase. Neuron 63:585–591. http://dx.doi.org/10.1016/j.neuron.2009.08.020.
  • Li C, MacDonald JIS, Hryciw T, Meakin SO. 2010. Nerve growth factor activation of the TrkA receptor induces cell death, by macropinocytosis, in medulloblastoma Daoy cells. J Neurochem 112:882–889. http://dx.doi.org/10.1111/j.1471-4159.2009.06507.x.
  • Commisso C, Davidson SM, Soydaner-Azeloglu RG, Parker SJ, Kamphorst JJ, Hackett S, Grabocka E, Nofal M, Drebin JA, Thompson CB, Rabinowitz JD, Metallo CM, Vander Heiden MG, Bar-Sagi D. 2013. Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497:633–637. http://dx.doi.org/10.1038/nature12138.
  • Donaldson JG, Porat-Shliom N, Cohen LA. 2009. Clathrin-independent endocytosis: a unique platform for cell signaling and PM remodeling. Cell Signal 21:1–6. http://dx.doi.org/10.1016/j.cellsig.2008.06.020.
  • Lim JP, Gleeson PA. 2011. Macropinocytosis: an endocytic pathway for internalising large gulps. Immunol Cell Biol 89:836–843. http://dx.doi.org/10.1038/icb.2011.20.
  • Lim J, Wang J, Kerr M, Teasdale R, Gleeson P. 2008. A role for SNX5 in the regulation of macropinocytosis. BMC Cell Biol 9:58. http://dx.doi.org/10.1186/1471-2121-9-58.
  • Swanson JA, Watts C. 1995. Macropinocytosis. Trends Cell Biol 5:424–428. http://dx.doi.org/10.1016/S0962-8924(00)89101-1.
  • Chi S, Kitanaka C, Noguchi K, Mochizuki T, Nagashima Y, Shirouzu M, Fujita H, Yoshida M, Chen W, Asai A, Himeno M, Yokoyama S, Kuchino Y. 1999. Oncogenic Ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells. Oncogene 18:2281–2290. http://dx.doi.org/10.1038/sj.onc.1202538.
  • Kaul A, Overmeyer JH, Maltese WA. 2007. Activated Ras induces cytoplasmic vacuolation and non-apoptotic death in glioblastoma cells via novel effector pathways. Cell Signal 19:1034–1043. http://dx.doi.org/10.1016/j.cellsig.2006.11.010.
  • Overmeyer JH, Kaul A, Johnson EE, Maltese WA. 2008. Active Ras triggers death in glioblastoma cells through hyperstimulation of macropinocytosis. Mol Cancer Res 6:965–977. http://dx.doi.org/10.1158/1541-7786.MCR-07-2036.
  • Overmeyer J, Young A, Bhanot H, Maltese W. 2011. A chalcone-related small molecule that induces methuosis, a novel form of non-apoptotic cell death, in glioblastoma cells. Mol Cancer 10:69. http://dx.doi.org/10.1186/1476-4598-10-69.
  • Bhanot H, Young AM, Overmeyer JH, Maltese WA. 2010. Induction of nonapoptotic cell death by activated Ras requires inverse regulation of Rac1 and Arf6. Mol Cancer Res 8:1358–1374. http://dx.doi.org/10.1158/1541-7786.MCR-10-0090.
  • Fernandez-Medarde A, Santos E. 2011. Ras in cancer and developmental diseases. Genes Cancer 2:344–358. http://dx.doi.org/10.1177/1947601911411084.
  • Parsons DW, Li M, Zhang X, Jones Sn Leary RJ, Lin JC-H, Boca SM, Carter H, Samayoa J, Bettegowda C, Gallia GL, Jallo GI, Binder ZA, Nikolsky Y, Hartigan J, Smith DR, Gerhard DS, Fults DW, VandenBerg S, Berger MS, Marie SKN, Shinjo SMO, Clara C, Phillips PC, Minturn JE, Biegel JA, Judkins AR, Resnick AC, Storm PB, Curran T, He Y, Rasheed BA, Friedman HS, Keir ST, McLendon R, Northcott PA, Taylor MD, Burger PC, Riggins GJ, Karchin R, Parmigiani G, Bigner DD, Yan H, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE. 2011. The genetic landscape of the childhood cancer medulloblastoma. Science 331:435–439. http://dx.doi.org/10.1126/science.1198056.
  • Kremer NE, D'Arcangelo G, Thomas SM, DeMarco M, Brugge JS, Halegoua S. 1991. Signal transduction by nerve growth factor and fibroblast growth factor in PC12 cells requires a sequence of src and ras. J Cell Biol 115:809–819. http://dx.doi.org/10.1083/jcb.115.3.809.
  • Meakin SO, MacDonald JIS, Gryz EA, Kubu CJ, Verdi JM. 1999. The signaling adapter protein FRS-2 competes with Shc for binding to TrkA: a model for discriminating proliferation and differentiation. J Biol Chem 274:9861–9870. http://dx.doi.org/10.1074/jbc.274.14.9861.
  • Tillement V, Lajoie-Mazenc I, Casanova A, Froment C, Penary M, Tovar D, Marquez R, Monsarrat B, Favre G, Pradines A. 2008. Phosphorylation of RhoB by CK1 impedes actin stress fiber organization and epidermal growth factor receptor stabilization. Exp Cell Res 314:2811–2821. http://dx.doi.org/10.1016/j.yexcr.2008.06.011.
  • Boukerche H, Su Z, Prévot C, Sarkar D, Fisher PB. 2008. mda-9/syntenin promotes metastasis in human melanoma cells by activating c-Src. Proc Natl Acad Sci U S A 105:15914–15919. http://dx.doi.org/10.1073/pnas.0808171105.
  • Deroanne CF, Hamelryckx D, Ho TTG, Lambert CA, Catroux P, Lapière CM, Nusgens BV. 2005. Cdc42 downregulates MMP-1 expression by inhibiting the ERK1/2 pathway. J Cell Sci 118:1173–1183. http://dx.doi.org/10.1242/jcs.01707.
  • Kutateladze TG. 2010. Translation of the phosphoinositide code by PI effectors. Nat Chem Biol 6:507–513. http://dx.doi.org/10.1038/nchembio.390.
  • Kasahara K, Nakayama Y, Sato I, Ikeda K, Hoshino M, Endo T, Yamaguchi N. 2007. Role of Src-family kinases in formation and trafficking of macropinosomes. J Cell Physiol 211:220–232. http://dx.doi.org/10.1002/jcp.20931.
  • Liberali P, Kakkonen E, Turacchio G, Valente C, Spaar A, Perinetti G, Böckmann RA, Corda D, Colanzi A, Marjomaki V, Luini A. 2008. The closure of PAK1-dependent macropinosomes requires the phosphorylation of CtBP1/BARS. EMBO J 27:970–981. http://dx.doi.org/10.1038/emboj.2008.59.
  • Swanson JA. 2008. Shaping cups into phagosomes and macropinosomes. Nat Rev Mol Cell Biol 9:639–649. http://dx.doi.org/10.1038/nrm2447.
  • Doherty GJ, McMahon HT. 2009. Mechanisms of endocytosis. Annu Rev Biochem 78:857–902. http://dx.doi.org/10.1146/annurev.biochem.78.081307.110540.
  • Talebian A, Robinson-Brookes K, MacDonald JIS, Meakin SO. 2013. Ras guanine nucleotide releasing factor 1 (RasGrf1) enhancement of Trk receptor mediated neurite outgrowth requires activation of both H-Ras and Rac. J Mol Neurosci 49:38–51. http://dx.doi.org/10.1007/s12031-012-9847-9.
  • Valdez G, Akmentin W, Philippidou P, Kuruvilla R, Ginty DD, Halegoua S. 2005. Pincher-mediated macroendocytosis underlies retrograde signaling by neurotrophin receptors. J Neurosci 25:5236–5247. http://dx.doi.org/10.1523/JNEUROSCI.5104-04.2005.
  • Chakrabarti K, Lin R, Schiller NI, Wang Y, Koubi D, Fan Y-X, Rudkin BB, Johnson GR, Schiller MR. 2005. Critical role for kalirin in nerve growth factor signaling through TrkA. Mol Cell Biol 25:5106–5118. http://dx.doi.org/10.1128/MCB.25.12.5106-5118.2005.
  • York RD, Yao H, Dillon T, Ellig CL, Eckert SP, McClecksy EW, Stork PJ. 1998. Rap1 mediates sustained MAP kinase activation induced by nerve growth factor. Nature 392:622–626. http://dx.doi.org/10.1038/33451.
  • Jeon C-Y, Moon M-Y, Kim J-H, Kim H-J, Kim J-G, Li Y, Jin J-K, Kim P-H, Kim H-C, Meier KE, Kim Y-S, Park J-B. 2012. Control of neurite outgrowth by RhoA inactivation. J Neurochem 120:684–698. http://dx.doi.org/10.1111/j.1471-4159.2011.07564.x.
  • Aoki K, Nakamura T, Matsuda M. 2004. Spatio-temporal regulation of Rac1 and Cdc42 activity during nerve growth factor-induced neurite outgrowth in PC12 Cells. J Biol Chem 279:713–719. http://dx.doi.org/10.1074/jbc.M306382200.
  • Ahmed I, Calle Y, Iwashita S, Nur-E-Kamal A. 2006. Role of Cdc42 in neurite outgrowth of PC12 cells and cerebellar granule neurons. Mol Cell Biochem 281:17–25. http://dx.doi.org/10.1007/s11010-006-0165-9.
  • Kozma R, Sarner S, Ahmed S, Lim L. 1997. Rho family GTPases and neuronal growth cone remodelling: relationship between increased complexity induced by Cdc42Hs, Rac1, and acetylcholine and collapse induced by RhoA and lysophosphatidic acid. Mol Cell Biol 17:1201–1211. http://dx.doi.org/10.1128/MCB.17.3.1201.
  • Nusser N, Gosmanova E, Zheng Y, Tigyi G. 2002. Nerve growth factor signals through TrkA, phosphatidylinositol 3-kinase, and Rac1 to inactivate RhoA during the initiation of neuronal differentiation of PC12 Cells. J Biol Chem 277:35840–35846. http://dx.doi.org/10.1074/jbc.M203617200.
  • Nakamura T, Komiya M, Sone K, Hirose F, Gotoh N, Morii H, Ohta Y, Mori M. 2002. Grit, a GTPase-activating protein for the Rho family, regulates neurite extension through association with the TrkA receptor and N-Shc and CrkL/Crk adapter molecules. Mol Cell Biol 22:8721–8734. http://dx.doi.org/10.1128/MCB.22.24.8721-8734.2002.
  • Parachoniak Christine A, Luo Y, Abella Jasmine V, Keen James H, Park M. 2011. GGA3 functions as a switch to promote Met receptor recycling, essential for sustained ERK and cell migration. Dev Cell 20:751–763. http://dx.doi.org/10.1016/j.devcel.2011.05.007.
  • Luiskandl S, Woller B, Schlauf M, Schmid JA, Herbst R. 2013. Endosomal trafficking of the receptor tyrosine kinase MuSK proceeds via clathrin-dependent pathways, Arf6 and actin. FEBS J 280:3281–3297. http://dx.doi.org/10.1111/febs.12309.
  • Donaldson JG, Jackson CL. 2011. ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nat Rev Mol Cell Biol 12:362–375. http://dx.doi.org/10.1038/nrm3117.
  • Porat-Shliom N, Kloog Y, Donaldson JG. 2008. A Unique platform for H-Ras signaling involving clathrin-independent endocytosis. Mol Biol Cell 19:765–775.
  • Ridley AJ. 2001. Rho family proteins: coordinating cell responses. Trends Cell Biol 11:471–477. http://dx.doi.org/10.1016/S0962-8924(01)02153-5.
  • Doughman RL, Firestone AJ, Wojtasiak ML, Bunce MW, Anderson RA. 2003. Membrane ruffling requires coordination between type Iα phosphatidylinositol phosphate kinase and Rac signaling. J Biol Chem 278:23036–23045. http://dx.doi.org/10.1074/jbc.M211397200.
  • Wells CM, Walmsley M, Ooi S, Tybulewicz V, Ridley AJ. 2004. Rac1-deficient macrophages exhibit defects in cell spreading and membrane ruffling but not migration. J Cell Sci 117:1259–1268. http://dx.doi.org/10.1242/jcs.00997.
  • Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, Klevernic I, Arthur JSC, Aless DR, Cohen P. 2007. The selectivity of protein kinase inhibitors: a further uptake. Biochem J 408:297–315. http://dx.doi.org/10.1042/BJ20070797.
  • Brown FD, Rozelle AL, Yin HL, Balla T, Donaldson JG. 2001. Phosphatidylinositol 4,5-bisphosphate and Arf6-regulated membrane traffic. J Cell Biol 154:1007–1018. http://dx.doi.org/10.1083/jcb.200103107.
  • Hibino K, Shibata T, Yanagida T, Sako Y. 2011. Activation kinetics of RAF protein in the ternary complex of RAF, RAS-GTP, and kinase on the plasma membrane of living cells: single-molecule imaging analysis. J Biol Chem 286:36460–36468. http://dx.doi.org/10.1074/jbc.M111.262675.
  • Wills MKB, Jones N. 2012. Teaching an old dogma new tricks: twenty years of Shc adaptor signalling. Biochem J 447:1–16. http://dx.doi.org/10.1042/BJ20120769.
  • Veithen A, Amyere M, Van Der Smissen P, Cupers P, Courtoy PJ. 1998. Regulation of macropinocytosis in v-Src-transformed fibroblasts: cyclic AMP selectively promotes regurgitation of macropinosomes. J Cell Sci 111:2329–2335.
  • Mettlen M, Platek A, Van Der Smissen P, Carpentier S, Amyere M, Lanzetti L, De Diesbach P, Tyteca D, Courtoy PJ. 2006. Src triggers circular ruffling and macropinocytosis at the apical surface of polarized MDCK cells. Traffic 7:589–603. http://dx.doi.org/10.1111/j.1600-0854.2006.00412.x.
  • Wooten MW, Seibenhener ML, Mamidipudi V, Diaz-Meco MT, Barker PA, Moscat J. 2001. The atypical protein kinase C-interacting protein p62 is a scaffold for NF-κB activation by nerve growth factor. J Biol Chem 276:7709–7712. http://dx.doi.org/10.1074/jbc.C000869200.
  • Roskoski J, R. 2005. Src kinase regulation by phosphorylation and dephosphorylation. Biochem Biophys Res Commun 331:1–14. http://dx.doi.org/10.1016/j.bbrc.2005.03.012.
  • Chellaiah MA, Schaller MD. 2009. Activation of Src kinase by protein-tyrosine phosphatase-PEST in osteoclasts: comparative analysis of the effects of bisphosphonate and protein-tyrosine phosphatase inhibitor on Src activation in vitro. J Cell Physiol 220:382–393. http://dx.doi.org/10.1002/jcp.21777.
  • Mandal A, Shahidullah M, Beimgraben C, Delamere NA. 2011. The effect of endothelin-1 on Src-family tyrosine kinases and Na, K-ATPase activity in porcine lens epithelium. J Cell Physiol 226:2555–2561. http://dx.doi.org/10.1002/jcp.22602.
  • Wennerberg K, Der CJ. 2004. Rho-family GTPases: it's not only Rac and Rho (and I like it). J Cell Sci 117:1301–1312. http://dx.doi.org/10.1242/jcs.01118.
  • Raftopoulou M, Hall A. 2004. Cell migration: Rho GTPases lead the way. Dev Biol 265:23–32. http://dx.doi.org/10.1016/j.ydbio.2003.06.003.
  • Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S. 1999. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science 285:895–898. http://dx.doi.org/10.1126/science.285.5429.895.
  • Feltrin D, Pertz O. 2012. Assessment of Rho GTPase signaling during neurite outgrowth. Methods Mol Biol 827:181–194. http://dx.doi.org/10.1007/978-1-61779-442-1_13.
  • Sun Y, Lim Y, Li F, Liu S, Lu J-J, Haberberger R, Zhong J-H, Zhou X-F. 2012. ProBDNF collapses neurite outgrowth of primary neurons by activating RhoA. PLoS One 7:e35883. http://dx.doi.org/10.1371/journal.pone.0035883.
  • Wills Zachary P, Mandel-Brehm C, Mardinly Alan R, McCord Alejandra E, Giger Roman J, Greenberg Michael E. 2012. The Nogo receptor family restricts synapse number in the developing hippocampus. Neuron 73:466–481. http://dx.doi.org/10.1016/j.neuron.2011.11.029.
  • Zhao CF, Liu Y, Ni YL, Yang JW, Hui HD, Sun ZB, Liu SJ. 2013. SCIRR39 promotes neurite extension via RhoA in NGF-induced PC12 cells. Dev Neurosci 35:373–383. http://dx.doi.org/10.1159/000350715.
  • Manning BD, Cantley LC. 2007. AKT/PKB signaling: navigating downstream. Cell 129:1261–1274. http://dx.doi.org/10.1016/j.cell.2007.06.009.
  • Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. 1997. Oncogenic Ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88:593–602. http://dx.doi.org/10.1016/S0092-8674(00)81902-9.
  • Overmeyer JH, Maltese WA. 2011. Death pathways triggered by activated Ras in cancer cells. Front Biosci 16:1693–1713. http://dx.doi.org/10.2741/3814.
  • D'Souza-Schorey C, Chavrier P. 2006. ARF proteins: roles in membrane traffic and beyond. Nat Rev Mol Cell Biol 7:347–358. http://dx.doi.org/10.1038/nrm1910.
  • Naslavsky N, Weigert R, Donaldson JG. 2004. Characterization of a nonclathrin endocytic pathway: membrane cargo and lipid requirements. Mol Biol Cell 15:3542–3552. http://dx.doi.org/10.1091/mbc.E04-02-0151.
  • Funakoshi Y, Hasegawa H, Kanaho Y. 2011. Regulation of PIP5K activity by Arf6 and its physiological significance. J Cell Physiol 226:888–895. http://dx.doi.org/10.1002/jcp.22482.
  • Ferrari C, Zippel R, Martegani E, Gnesutta N, Carrera V, Sturani E. 1994. Expression of two different products of CDC25Mm, a mammalian Ras activator, during development of mouse brain. Exp Cell Res 210:353–357. http://dx.doi.org/10.1006/excr.1994.1048.
  • Engelman JA, Luo J, Cantley LC. 2006. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 7:606–619. http://dx.doi.org/10.1038/nrg1879.
  • Jovanovic OA, Brown FD, Donaldson JG. 2006. An effector domain mutant of Arf6 implicates phospholipase D in endosomal membrane recycling. Mol Biol Cell 17:327–335.
  • Donepudi M, Resh MD. 2008. c-Src trafficking and co-localization with the EGF receptor promotes EGF ligand-independent EGF receptor activation and signaling. Cell Signal 20:1359–1367. http://dx.doi.org/10.1016/j.cellsig.2008.03.007.
  • Saito Y, Tsuzuki K, Yamada N, Okado H, Miwa A, Goto F, Ozawa S. 2003. Transfer of NMDAR2 cDNAs increases endogenous NMDAR1 protein and induces expression of functional NMDA receptors in PC12 cells. Mol Brain Res 110:159–168. http://dx.doi.org/10.1016/S0169-328X(02)00548-X.
  • Obara Y, Labudda K, Dillon TJ, Stork PJS. 2004. PKA phosphorylation of Src mediates Rap1 activation in NGF and cAMP signaling in PC12 cells. J Cell Sci 117:6085–6094. http://dx.doi.org/10.1242/jcs.01527.
  • Arthur DB, Akassoglou K, Insel PA. 2006. P2Y2 and TrkA receptors interact with Src family kinase for neuronal differentiation. Biochem Biophys Res Commun 347:678–682. http://dx.doi.org/10.1016/j.bbrc.2006.06.141.
  • Tsuruda A, Suzuki S, Maekawa T, Oka S. 2004. Constitutively active Src facilitates NGF-induced phosphorylation of TrkA and causes enhancement of the MAPK signaling in SK-N-MC cells. FEBS Lett 560:215–220. http://dx.doi.org/10.1016/S0014-5793(04)00115-2.
  • Spiering D, Hodgson L. 2011. Dynamics of the Rho-family small GTPases in actin regulation and motility. Cell Adhesion Migration 5:170–180. http://dx.doi.org/10.4161/cam.5.2.14403.
  • Knippschild U, Gocht A, Wolff S, Huber N, Löhler J, Stöter M. 2005. The casein kinase 1 family: participation in multiple cellular processes in eukaryotes. Cell Signal 17:675–689. http://dx.doi.org/10.1016/j.cellsig.2004.12.011.
  • Kurokawa K, Matsuda M. 2005. Localized RhoA activation as a requirement for the induction of membrane ruffling. Mol Biol Cell 16:4294–4303. http://dx.doi.org/10.1091/mbc.E04-12-1076.
  • Vander Heiden MG, Cantley LC, Thompson CB. 2009. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–1033. http://dx.doi.org/10.1126/science.1160809.
  • Yung Yun C, Stoddard Nicole C, Mirendil H, Chun J. 2015. Lysophosphatidic acid signaling in the nervous system. Neuron 85:669–682. http://dx.doi.org/10.1016/j.neuron.2015.01.009.

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