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Adaptor proteins in protein kinase C-mediated signal transduction

Oncogene volume 20, pages 6339–6347 (2001)Cite this article

Abstract

Spatial and temporal organization of signal transduction is essential in determining the speed and precision by which signaling events occur. Adaptor proteins are key to organizing signaling enzymes near their select substrates and away from others in order to optimize precision and speed of response. Here, we describe the role of adaptor proteins in determining the specific function of individual protein kinase C (PKC) isozymes. These isozyme-selective proteins were called collectively RACKs (receptors for activated C-kinase). The role of RACKs in PKC-mediated signaling was determined using isozyme-specific inhibitors and activators of the binding of each isozyme to its respective RACK. In addition to anchoring activated PKC isozymes, RACKs anchor other signaling enzymes. RACK1, the anchoring protein for activated βIIPKC, binds for example, Src tyrosine kinase, integrin, and phosphodiesterase. RACK2, the εPKC-specific RACK, is a coated-vesicle protein and thus is involved in vesicular release and cell–cell communication. Therefore, RACKs are not only adaptors for PKC, but also serve as adaptor proteins for several other signaling enzymes. Because at least some of the proteins that bind to RACKs, including PKC itself, regulate cell growth, modulating their interactions with RACKs may help elucidate signaling pathways leading to carcinogenesis and could result in the identification of novel therapeutic targets.

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References

  • Aley KO, Messing RO, Mochly-Rosen D, Levine JD . 2000 J. Neurosci. 20: 4680–4685

  • Berns H, Humar R, Hengerer B, Kiefen FN, Battegay EJ . 2000 FASEB J. 14: 2549–2558

  • Borner C, Wyss R, Regazzi R, Eppenberger U, Fabbro D . 1987 Int. J. Cancer 40: 344–348

  • Burack WR, Shaw AS . 2000 Curr. Opin. Cell. Biol. 12: 211–216

  • Carpenter D, Jackson T, Hanley MR . 1987 Nature 325: 107–108

  • Castagna M, Takai Y, Kaibuchi K, Sano K, Kikkawa U, Nishizuka Y . 1982 J. Biol. Chem. 257: 7847–7851

  • Chang BY, Chiang M, Cartwright CA . 2001 J. Biol. Chem. 276: 20346–20356

  • Chang BY, Conroy KB, Machleder EM, Cartwright CA . 1998 Mol. Cell. Biol. 18: 3245–3256

  • Chen C, Mochly-Rosen D . 2001 J. Mol. Cell. Cardiol. 33: 581–585

  • Choi KY, Satterberg B, Lyons DM, Elion EA . 1994 Cell 78: 499–512

  • Csukai M, Chen CH, De Matteis MA, Mochly-Rosen D . 1997 J. Biol. Chem. 272: 29200–29206

  • Csukai M, Mochly-Rosen D . 1999 Pharmacol. Res. 39: 253–259

  • De Camilli P, Takei K, McPherson PS . 1995 Curr. Opin. Neurobiol. 5: 559–565

  • De Matteis MA, Santini G, Kahn RA, Di Tullio G, Luini A . 1993 Nature 364: 818–821

  • Dempsey EC, Newton AC, Mochly-Rosen D, Fields AP, Reyland ME, Insel PA, Messing RO . 2000 Am. J. Physiol. Lung Cell. Mol. Physiol. 279: L429–L438

  • Disatnik MH, Buraggi G, Mochly-Rosen D . 1994a Exp. Cell. Res. 210: 287–297

  • Disatnik MH, Hernandez-Sotomayor SM, Jones G, Carpenter G, Mochly-Rosen D . 1994b Proc. Natl. Acad. Sci. USA 91: 559–563

  • Disatnik MH, Winnier AR, Mochly-Rosen D, Arteaga CL . 1994c Cell. Growth Differ. 5: 873–880

  • Dorn GW, 2nd, Souroujon MC, Liron T, Chen CH, Gray MO, Zhou HZ, Csukai M, Wu G, Lorenz JN, Mochly-Rosen D . 1999 Proc. Natl. Acad. Sci. USA 96: 12798–12803

  • Fong HK, Amatruda TT, 3rd, Birren BW, Simon MI . 1987 Proc. Natl. Acad. Sci. USA 84: 3792–3796

  • Garcia-Higuera I, Fenoglio J, Li Y, Lewis C, Panchenko MP, Reiner O, Smith TF, Neer EJ . 1996 Biochemistry 35: 13985–13994

  • Gawler DJ, Zhang LJ, Reedijk M, Tung PS, Moran MF . 1995 Oncogene 10: 817–825

  • Gokmen-Polar Y, Murray NR, Velasco MA, Gatalica Z, Fields AP . 2001 Cancer Res. 61: 1375–1381

  • Gray MO, Karliner JS, Mochly-Rosen D . 1997 J. Biol. Chem. 272: 30945–30951

  • Harrison-Lavoie KJ, Lewis VA, Hynes GM, Collison KS, Nutland E, Willison KR . 1993 EMBO J. 12: 2847–2853

  • Hibbs ML, Jakes S, Stacker SA, Wallace RW, Springer TA . 1991 J. Exp. Med. 174: 1227–1238

  • Hocevar BA, Fields AP . 1991 J. Biol. Chem. 266: 28–33

  • Hu K, Mochly-Rosen D, Boutjdir M . 2000 Am. J. Physiol. Heart Circ. Physiol. 279: H2658–H2664

  • Hubbard MJ, Cohen P . 1993 TIBS 18: 172–177

  • Hundle B, McMahon T, Dadgar J, Chen CH, Mochly-Rosen D, Messing RO . 1997 J. Biol. Chem. 272: 15028–15035

  • Irby RB, Yeatman TJ . 2000 Oncogene 19: 5636–5642

  • Jaken S, Parker PJ . 2000 Bioessays 22: 245–254

  • Johnson JA, Gray MO, Chen CH, Mochly-Rosen D . 1996a J. Biol. Chem. 271: 24962–24966

  • Johnson JA, Gray MO, Karliner JS, Chen CH, Mochly-Rosen D . 1996b Circ. Res. 79: 1086–1099

  • Johnson JA, Mochly-Rosen D . 1995 Circ. Res. 76: 654–663

  • Kholodenko BN, Hoek JB, Westerhoff HV . 2000 Trends Cell. Biol. 10: 173–178

  • Kieff E . 1996 Epstein-Barr Virus and its Replication Lippincott-Raven Publishers, Philadelphia 2343–2396

    Google Scholar 

  • Kiley S, Schaap D, Parker P, Hsieh L, Jaken S . 1990 J. Biol. Chem. 265: 15704–15712

  • Kiley SC, Clark KJ, Duddy SK, Welch DR, Jaken S . 1999a Oncogene 18: 6748–6757

  • Kiley SC, Clark KJ, Goodnough M, Welch DR, Jaken S . 1999b Cancer Res. 59: 3230–3238

  • Knauf JA, Elisei R, Mochly-Rosen D, Liron T, Chen XN, Gonsky R, Korenberg JR, Fagin JA . 1999 J. Biol. Chem. 274: 23414–23425

  • Koehler JA, Moran MF . 2001 Biochem. Biophys. Res. Commun. 283: 888–895

  • Lemmon MA, Ferguson KM, Schlessinger J . 1996 Cell 85: 621–624

  • Levin DE, Errede B . 1995 Curr. Opin. Cell. Biol. 7: 197–202

  • Liliental J, Chang DD . 1998 J. Biol. Chem. 273: 2379–2383

  • Liu GS, Cohen MV, Mochly-Rosen D, Downey JM . 1999 J. Mol. Cell. Cardiol. 31: 1937–1948

  • Livneh E, Shimon T, Bechor E, Doki Y, Schieren I, Weinstein IB . 1996 Oncogene 12: 1545–1555

  • Maeda T, Lloyd RV . 1993 Lab. Invest. 68: 472–480

  • Mayne GC, Murray AW . 1998 J. Biol. Chem. 273: 24115–24121

  • Mellor H, Parker PJ . 1998 Biochem. J. 332: 281–292

  • Moasser MM, Srethapakdi M, Sachar KS, Kraker AJ, Rosen N . 1999 Cancer Res. 59: 6145–6152

  • Mochly-Rosen D . 1995 Science 268: 247–251

  • Mochly-Rosen D, Henrich CJ, Cheever L, Khaner H, Simpson PC . 1990 Cell. Regul. 1: 693–706

  • Mochly-Rosen D, Wu G, Hahn H, Osinska H, Liron T, Lorenz JN, Yatani A, Robbins J, Dorn GW, 2nd . 2000 Circ. Res. 86: 1173–1179

  • Mourton T, Hellberg CB, Burden-Gulley SM, Hinman J, Rhee A, Brady-Kalnay SM . 2001 J. Biol. Chem. 276: 14896–14901

  • Myklebust JH, Josefsen D, Blomhoff HK, Levy OF, Naderi S, Reed JC, Smeland EB . 1999 J. Cell. Physiol. 180: 71–80

  • Nakaigawa N, Hirai S, Mizuno K, Shuin T, Hosaka M, Ohno S . 1996 Biochem. Biophys. Res. Commun. 222: 95–100

  • Neer EJ, Schmidt CJ, Nambudripad R, Smith TF . 1994 Nature 371: 297–300

  • Nishizuka Y . 1988 Nature 334: 661–665

  • Parker PJ, Kour G, Marais RM, Mitchell F, Pears C, Schaap D, Stabel S, Webster C . 1989 Mol. Cell. Endocrinol. 65: 1–11

  • Pass JM, Zheng Y, Wead WB, Zhang J, Li RC, Bolli R, Ping P . 2001 Am. J. Physiol. Heart Circ. Physiol. 280: H946–H955

  • Pawson T, Scott JD . 1997 Science 278: 2075–2080

  • Reinhardt J, Wolff T . 2000 Vet. Microbiol. 74: 87–100

  • Reszka AA, Hayashi Y, Horwitz AF . 1992 J. Cell. Biol. 117: 1321–1330

  • Robinson PJ, Sontag JM, Liu JP, Fykse EM, Slaughter C, McMahon H, Sudhof TC . 1993 Nature 365: 163–166

  • Rodriguez MM, Ron D, Touhara K, Chen CH, Mochly-Rosen D . 1999 Biochemistry 38: 13787–13794

  • Rodriguez-Fernandez JL, Rozengurt E . 1996 J. Biol. Chem. 271: 27895–27901

  • Ron D, Chen CH, Caldwell J, Jamieson L, Orr E, Mochly-Rosen D . 1994 Proc. Natl. Acad. Sci. USA 91: 839–843

  • Ron D, Jiang Z, Yao L, Vagts A, Diamond I, Gordon A . 1999 J. Biol. Chem. 274: 27039–27046

  • Ron D, Luo J, Mochly-Rosen D . 1995 J. Biol. Chem. 270: 24180–24187

  • Ron D, Mochly-Rosen D . 1995 Proc. Natl. Acad. Sci. USA 92: 492–496

  • Sasaguri T, Kosaka C, Hirata M, Masuda J, Shimokado K, Fujishima M, Ogata J . 1993 Exp. Cell. Res. 208: 311–320

  • Schwartz GK, Jiang J, Kelsen D, Albino AP . 1993 J. Natl. Cancer Inst. 85: 402–407

  • Smith PR, de Jesus O, Turner D, Hollyoake M, Karstegl CE, Griffin BE, Karran L, Wang Y, Hayward SD, Farrell PJ . 2000 J. Virol. 74: 3082–3092

  • Sondek J, Bohm A, Lambright DG, Hamm HE, Sigler PB . 1996 Nature 379: 369–374

  • Souroujon MC, Mochly-Rosen D . 1998 Nat. Biotechnol. 16: 919–924

  • Srivastava RK, Srivastava AR, Cho-Chung YS, Longo DL . 1999 Oncogene 18: 1755–1763

  • Stenbeck G, Harter C, Brecht A, Herrmann D, Lottspeich F, Orci L, Wieland FT . 1993 EMBO J. 12: 2841–2845

  • Thompson EB, Medh RD, Zhou F, Ayala-Torres S, Ansari N, Zhang W, Johnson BH . 1999 J. Steroid Biochem. Mol. Biol. 69: 453–461

  • Thompson LJ, Fields AP . 1996 J. Biol. Chem. 271: 15045–15053

  • Touhara K, Inglese J, Pitcher JA, Shaw G, Lefkowitz RJ . 1994 J. Biol. Chem. 269: 10217–10220

  • Tsai JH, Hsieh YS, Kuo SJ, Chen ST, Yu SY, Huang CY, Chang AC, Wang YW, Tsai MT, Liu JY . 2000 Cancer Lett. 161: 171–175

  • Vallete A, Gas N, Roubinet F, Dupont M, Bayard F . 1987 Cancer Res. 47: 1615–1620

  • van der Geer P, Henkemeyer M, Jacks T, Pawson T . 1997 Mol. Cell. Biol. 17: 1840–1847

  • Wall MA, Coleman DE, Lee E, Iniguez-Lluhi JA, Posner BA, Gilman AG, Sprang SR . 1995 Cell 83: 1047–1058

  • Watanabe T, Ono Y, Taniyama Y, Hazama K, Igarashi K, Ogita K, Kikkawa U, Nishizuka Y . 1992 Proc. Natl. Acad. Sci. USA 89: 10159–10163

  • Wu HL, Albrightson C, Nambi P . 1999 Peptides 20: 675–678

  • Wyss R, Fabbro D, Regazzi R, Borner C, Takahashi A, Eppenberger U . 1987 Anticancer Res. 7: 721–727

  • Yarwood SJ, Steele MR, Scotland G, Houslay MD, Bolger GB . 1999 J. Biol. Chem. 274: 14909–14917

  • Yedovitzky M, Mochly-Rosen D, Johnson JA, Gray MO, Ron D, Abramovitch E, Cerasi E, Nesher R . 1997 J. Biol. Chem. 272: 1417–1420

  • Zhang ZH, Johnson JA, Chen L, El-Sherif N, Mochly-Rosen D, Boutjdir M . 1997 Circ. Res. 80: 720–729

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Acknowledgements

We are grateful to Dr Adrienne S Gordon for her advice and discussions and to Dr Marie-Helene Disatnik for the help with the GAP studies. DS is an Ares-Serono fellow. This work was supported in part by California Breast Cancer Research Program of the University of California #6JB0056 to DMR.

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  1. Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA

    Deborah Schechtman & Daria Mochly-Rosen

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Correspondence to Daria Mochly-Rosen.

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Schechtman, D., Mochly-Rosen, D. Adaptor proteins in protein kinase C-mediated signal transduction. Oncogene 20, 6339–6347 (2001). https://doi.org/10.1038/sj.onc.1204778

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