Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Nck/Dock: an adapter between cell surface receptors and the actin cytoskeleton

Abstract

In response to extracellular signals, cell surface receptors engage in connections with multiple intracellular signaling pathways, leading to the cellular responses such as survival, migration, proliferation and differentiation. The ‘pY→SH2/SH3→effector’ connection is a frequently used scheme by many cell surface receptors, in which SH2/SH3-containing adapters connect protein tyrosine phosphorylation to a variety of downstream effector pathways. Following the initial landmark finding that Grb2 adapter links the receptors to the Ras pathway leading to DNA synthesis, recent studies have revealed that the biological function of the SH2/SH3 adapter Nck/Dock is to link cell surface receptors to the actin cytoskeleton. For example, in the evolutionarily-conserved signaling network, GEF-Rac-Nck-Pak, Nck ‘fixes up’ the interaction of Pak with its upstream activator, Rac. The activated Pak then regulates the cytoskeletal dynamics. The fact that the majority of the more than 20 Nck-SH3-associated effectors are regulators of the actin cytoskeleton suggests that Nck/Dock regulates, via binding to distinct effectors, various cell type-specific motogenic responses. This review focuses on our current understanding of Nck/Dock function. Due to the number and complexity of the terminologies used in this review, a ‘Glossary of Terms’ is provided to help reduce confusions.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Adler CE, Miyoshi-Akiyama T, Aleman LM, Tanaka M, Smith JM, Mayer BJ . 2000 J. Biol. Chem. 275: 36472–36438

  • Anand-Apte B, Zetter B, Viswanathan A, Qui RG, Chen J, Ruggieri R, Symons M . 1997 J. Biol. Chem. 272: 30688–30692

  • Anton IM, Lu W, Mayer BJ, Ramesh N, Geha RS . 1998 J. Biol. Chem. 273: 20992–20995

  • Bagrodia S, Cerion RA . 1999 Trends Cell. Biol. 9: 350–355

  • Bagrodia S, Taylor SJ, Jordon KA, Van Aelst L, Cerione RA . 1998 J. Biol. Chem. 273: 23633–23636

  • Becker E, Huynh-Do U, Holland S, Pawson T, Daniel TO, Skolnik EY . 2000 Mol. Cell. Biol. 20: 1537–1545

  • Birge PB, Knudsen BS, Besser B, Hanafusa H . 1996 Genes Cells 1: 595–613

  • Bokoch GM, Wang Y, Bohl BP, Sells MA, Quilliam LA, Knaus UG . 1996 J. Biol. Chem. 271: 25746–25749

  • Bokoch GM, Reilly AM, Daniels RH, King CC, Olivera A, Spiegel S, Knaus UG . 1998 J. Biol. Chem. 273: 8137–8144

  • Bornfeldt KE, Raines EW, Nakano T, Graves LM, Krebs EG, Ross R . 1994 J. Clin. Invest. 93: 1266–1274

  • Bornfeldt KE, Graves LM, Raines EW, Igarashi Y, Wayman G, Yamamura S, Yatomi Y, Sidhu JS, Krebs EG, Hakomori S . 1995 J. Cell. Biol. 130: 193–206

  • Braverman LE, Quilliam LA . 1999 J. Biol. Chem. 247: 5542–4459

  • Buchanan PG, Elliot CM, Gibbs M, Exton JH . 2000 J. Biol. Chem. 275: 9742–9748

  • Bubeck Wardenburg J, Pappu R, Bu J-Y, Mayer B, Chernoff J, Straus D, Chan AC . 1998 Immunity 9: 607–616

  • Chen M, She H, Davis EM, Spicer CM, Kim L, Ren R, Le Beau M, Li W . 1998 J. Biol. Chem. 273: 25171–25178

  • Chen M, She H, Kim A, Woodley DT, Li W . 2000 Mol. Cell. Biol. 20: 7867–7880

  • Cheresh DA, Leng J, Klemke RL . 1999 J. Cell. Biol. 146: 1107–1116

  • Chou MM, Fajardo JE, Hanafusa H . 1992 Mol. Cell. Biol. 12: 5834–5842

  • Clark SG, Stern MJ, Horvitz HR . 1992 Nature 356: 340–344

  • Clemens JC, Ursuliak Z, Clemens KK, Price JV, Dixon JE . 1996 J. Biol. Chem. 271: 17002–17005

  • Daniels RH, Hall PS, Bokoch GM . 1998 EMBO J. 17: 754–764

  • Debant A, Serra-Pages C, Seipel K, O'Brien S, Tang M, Park SH, Streuli M . 1996 Proc. Natl. Acad. Sci. USA 93: 5466–5471

  • Desai CJ, Garrity PA, Keshishian H, Zipursky SL, Zinn K . 1999 Development 126: 1527–1535

  • Dharmawardhane S, Schürmann A, Sells MA, Chernoff J, Schmid SL, Bokoch GM . 2000 Mol. Biol. Cell 11: 3341–3352

  • Drescher D . 1997 Curr. Biol. 7: R799–R807

  • Duel TF, Kawahara RS, Mustoe TA, Pierce GF . 1991 Annu. Rev. Med. 42: 567–584

  • Ellis C, Kasmi F, Ganju P, Walls E, Panayotou G, Reith AD . 1996 Oncogene 12: 1727–1736

  • Feng GS, Ouyang YB, Hu DP, Shi ZO, Gentz R, Ni J . 1996 J. Biol. Chem. 271: 12129–12132

  • Finco TS, Kadlecek T, Zhang W, Samelson LE, Weiss A . 1998 Immunity 9: 617–626

  • Flanagan JG, Vanderhaeghen P . 1998 Annu. Rev. Neurosci. 21: 309–345

  • Frischknecht F, Moreau V, Rottger S, Gonfloni S, Reckmann I, Superti-Furga G, Way M . 1999 Nature 401: 926–929

  • Galisteo ML, Chernoff J, Su YC, Skolnik EY, Schlessinger J . 1996 J. Biol. Chem. 271: 20997–21000

  • Garrity PA, Lee CH, Salecker I, Robertson HC, Desai CJ, Zinn K, Zipursky SL . 1999 Neuron 22: 707–717

  • Garrity PA, Rao Y, Salecker I, McGlade J, Pawson T, Zipursky SL . 1996 Cell 85: 639–650

  • Godwin SL, Soltoff SP . 1997 J. Biol. Chem. 272: 11307–11312

  • Guo D, Jia Q, Song HY, Warren RS, Donner DB . 1995 J. Biol. Chem. 270: 6729–6733

  • Higgs HN, Pollard TD . 1999 J. Biol. Chem. 274: 32531–32544

  • Hing H, Xiao J, Harden N, Lim L, Zipursky SL . 1999 Cell 97: 853–863

  • Hock B, Bohme B, Karn T, Feller S, Rubsamen-Waigmann H, Strebhardt K . 1998 Oncogene 17: 255–260

  • Holland SJ, Gale NW, Gish GD, Roth RA, Songyang Z, Cantley LC, Henkemeyer M, Yancopoulos GD, Pawson T . 1997 EMBO J. 16: 3877–3888

  • Holland SJ, Peles E, Pawson T, Schlessinger J . 1998 Curr. Opin. Neurobiol. 8: 117–127

  • Hummel T, Leifker K, Klambt C . 2000 Genes Dev. 14: 863–873

  • Igarashi K, Isohara T, Kato T, Shigeta K, Yamano T, Uno I . 1998 Biochem. Biophys. Res. Commun. 246: 95–99

  • Jackman JK, Motto DG, Sun O, Tanemoto M, Turck CW, Peltz GA, Koretzky P, Findell R . 1995 J. Biol. Chem. 270: 7029–7032

  • Jones SM, Kazlauskas A . 2000 Oncogene 19: 5558–5567

  • Joneson T, McDonough M, Bar-Sagi D, Van Aelst L . 1996 Science 274: 1374–1376

  • Kiosses WB, Daniels RH, Otey C, Bokoch GM, Schwartz MA . 1999 J. Cell. Biol. 147: 831–844

  • Kiyokawa E, Hashimoto Y, Kobayashi S, Sugimura H, Kurata T, Matsuda M . 1998a Genes Dev. 12: 3331–3336

  • Kiyokawa E, Hashimoto Y, Kurata T, Sugimura H, Matsuda M . 1998b J. Biol. Chem. 273: 24479–24484

  • Kitamura T, Kitamura Y, Yonezawa K, Totty NF, Gout I, Hara K, Waterfield MD, Sakaue M, Ogawa W, Kasuga M . 1996 Biophys. Res. Commun. 219: 509–514

  • Kitamura Y, Kitamura T, Sakaue H, Maeda T, Ueno H, Nisho S, Ohno S, Osada S, Sakaue M, Ogawa W, Kasuga M . 1997 Eur. J. Biochem. 322: 873–878

  • Knaus UG, Bokoch GM . 1998 Intl. J. Biochem. Cell. Biol. 30: 857–862

  • Kroll J, Waltenberger J . 1997 J. Biol. Chem. 252: 32421–32527

  • Ku GM, Yablonski D, Manser E, Lim L, Weiss A . 2001 EMBO J. 20: 457–465

  • Kundra V, Escobedo JA, Kazlauskas A, Kim HK, Rhee SG, Williams LT, Zetter B . 1994 Nature 367: 474–476

  • Kyriakis JM . 1999 J. Biol. Chem. 274: 5259–5262

  • Lamarche N, Tapon N, Stowers, Burbelo PD, Aspenstrom P, Bridges T, Chant J, Hall A . 1996 Cell 87: 519–529

  • Lehmann JM, Riethmuller G, Johson JP . 1990 Nucl. Acids Res. 18: 1048

  • Li W, Hu P, Skolnik EY, Ullrich A, Schlessinger J . 1992 Mol. Cell. Biol. 12: 5824–5833

  • Li W, She H . 2000 Hist. Histopath. 15: 947–955

  • Lim WA, Richards FM, Fox RO . 1994 Nature 372: 375–379

  • Lin JA, Weiss, Finco TS . 1999 J. Biol. Chem. 274: 28861–28864

  • Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J . 1992 Cell 70: 431–442

  • Lu S, Katz, Gupta R, Mayer BJ . 1997 Curr. Biol. 7: 85–94

  • Lu W, Mayer BJ . 1999 Oncogene 18: 797–806

  • Manser E, Huang HY, Loo TH, Chen XQ, Dong JM, Leung T, Lim L . 1997 Mol. Cell. Biol. 17: 1129–1143

  • Manser E, Loo TH, Koh CG, Zhao ZS, Chen XQ, Tan L, Tan I, Leung T, Lim L . 1998 Mol. Cell 1: 183–192

  • Margolis B . 1994 Prog. Biophys. Mol. Biol. 62: 223–244

  • Margolis B, Mohammaddi M, Ullrich A, Schlessinger J . 1992 Proc. Natl. Acad. Sci. USA 89: 8894–8898

  • Mayer BJ . 1999 Mol. Biotechnol. 13: 201–213

  • Mayer BJ . 2001 J. Cell. Sci. 114: 1253–1263

  • McCarty JH . 1998 Bioessays 20: 913–921

  • Meisenhelder J, Hunter T . 1992 Mol. Cell. Biol. 12: 5843–5856

  • Moreau V, Frischknecht F, Reckmann I, Vincentelli R, Rabut G, Stewart D, Way M . 2000 Nat. Cell. Biol. 2: 441–448

  • Morrione A . 2000 Int. J. Mol. Med. 5: 151–144

  • Newsome TP, Schmidt S, Dietzl G, Keleman K, Asling B, Debant A, Dickson BJ . 2000 Cell 101: 283–294

  • Nishimura R, Li W, Kashishian A, Mondino A, Zhou M, Cooper J, Schlessinger J . 1993 Mol. Cell. Biol. 13: 6889–6896

  • Nobes CD, Hawkins P, Stephens L, Hall A . 1995 J. Cell. Sci. 108: 225–233

  • Obermeier A, Ahmed S, Manser E, Yen SC, Hall SC, Lim L . 1998 EMBO J. 17: 4238–4339

  • O'Leary DD, Wilkinson DG . 1999 Curr. Opin. Neurobiol. 9: 65–73

  • Olivier JP, Raabe T, Henkemeyer M, Dickson B, Mbamalu G, Margolis B, Schlessinger J, Hafen E, Pawson T . 1993 Cell 73: 179–191

  • Pandey A, Lazar DF, Saltiel AR, Dixit VM . 1994 J. Biol. Chem. 269: 30154–30157

  • Pandey A, Duan H, Dixit VM . 1995 J. Biol. Chem. 270: 19201–19204

  • Park D . 1997 Mol. Cells (Korea) 7: 231–236

  • Park D, Rhee SG . 1992 Mol. Cell. Biol. 12: 5816–5823

  • Pawson T . 1995 Nature 373: 573–580

  • Pierce GF, Mustoe TA . 1995 Annu. Rev. Med. 46: 467–481

  • Quilliam LA, Lambert QT, Mickelson-Young LA, Westwick JK, Sparks BK, Jenkins NA, Gilbert DJ, Copeland NG, Der CJ . 1996 J. Biol. Chem. 271: 28772–28776

  • Rao Y, Zipursky SL . 1998 Proc. Natl. Acad. Sci. USA 95: 2077–2082

  • Ridley AJ, Hall A . 1992 Cell 70: 389–399

  • Rivero-Lezcano OM, Sameshima JH, Marcilla A, Robbins KC . 1995 J. Biol. Chem. 269: 17363–17366

  • Rosenkranz S, DeMali KA, Gelderloos JA, Bazenet C, Kazlauskas A . 1999 J. Biol. Chem. 274: 28335–28343

  • Ross R . 1993 Nature 362: 908–809

  • Ruan W, Pang P, Rao Y . 1999 Neuron 24: 595–605

  • Schlessinger J . 1994 Curr. Opin. Genet. Dev. 4: 25–30

  • Schmucker D, Clemens JC, Shu H, Worby CA, Xiao J, Muda M, Dixon JE, Zipursky SL . 2000 Cell 101: 671–684

  • Sells MA, Chernoff J . 1997 Trends Cell. Biol. 7: 162–167

  • Sells MA, Boyd JT, Chernoff J . 1999 J. Cell. Biol. 145: 837–849

  • Sells MA, Pfaff A, Chernoff J . 2000 J. Cell. Biol. 151: 1449–1457

  • Smith JM, Katz S, Mayer BJ . 1999 J. Biol. Chem. 274: 27956–27962

  • Song H-J, Poo M-M . 1999 Curr. Opin. Neurobiol. 9: 355–363

  • Stein E, Huynh-Do U, Lane AA, Cerretti DP, Daniel TO . 1998 J. Biol. Chem. 273: 1303–1308

  • Steven R, Kubiseski TJ, Zheng H, Kulkarni S, Mancillas J, Ruiz Morales A, Hogue CW, Pawson T, Culotti T . 1998 Cell 92: 785–795

  • Stoletov KV, Ratcliffe KE, Spring SC, Terman BI . 2001 J. Biol. Chem. 276: 22748–22755

  • Su YC, Han J, Xu S, Cobb M, Skolnik EY . 1997 EMBO J. 16: 1279–1290

  • Su YC, Maurel-Zaffran C, Treisman JE, Skolnik EY . 2000 Mol. Cell. Biol. 20: 4736–4744

  • Treisman JE, Ito N, Rubin GM . 1997 Gene 186: 119–125

  • Tu Y, Kucik DF, Wu C . 2001 FEBS Lett. 491: 193–199

  • Tu Y, Li F, Goicoechea S, Wu C . 1999 Mol. Cell. Biol. 19: 2425–2434

  • Tu Y, Li F, Wu C . 1998 Mol. Biol. Cell 9: 3367–3382

  • Turner CE, Brown MC, Perrotta JA, Riedy MC, Nikolopoulos SN, McDonald AR, Bagrodia S, Thomas S, Leventhal PS . 1999 J. Cell. Biol. 145: 851–863

  • Wahl S, Barth H, Ciossek T, Aktories K, Mueller BK . 2000 J. Cell. Biol. 149: 263–270

  • Westwick JK, Lambert QT, Clark GJ, Symons M, Van Aelst L, Pestell RG, Der CJ . 1997 Mol. Cell. Biol. 17: 1324–1335

  • Wu C . 1999 J. Cell. Sci. 112: 4485–4489

  • Yablonski D, Kane LP, Qian D, Weiss A . 1998 EMBO J. 17: 5647–5657

  • Yamakawa K, Huot YK, Haendelt M, Hubert R, Chen XN, Lyons GE, Korenberg JR . 1998 Hum. Mol. Genet. 7: 227–237

  • Yoshii S . et al. 1999 Oncogene 18: 5680–5690

  • Zhao Z-S, Manser E, Chen X-Q, Chong C, Leung T, Lim L . 1998 Mol. Cell. Biol. 18: 2153–2163

  • Zhao ZS, Manser E, Lim L . 2000a Mol. Cell. Biol. 20: 3906–3917

  • Zhao ZS, Manser E, Loo TH, Lim L . 2000b Mol. Cell. Biol. 20: 6354–6363

  • Zhang S, Sloan-Lancaster JJ, Kitchen J, Trible RP, Samelson LE . 1998a Cell 92: 83–92

  • Zhang W, Trible RP, Samelson LE . 1998b Immunity 9: 239–246

  • Zhang W, Irvin BJ, Trible RP, Abraham RT, Samelson LE . 1999 Int. Immunol. 11: 943–950

  • Zigmond SH . 2000 J. Cell. Biol. 150: F117–F122

Download references

Acknowledgements

This study was supported by NIH Grants CA65567 (to W Lei) and AR46538 (to DT Woodley).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wei Li.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, W., Fan, J. & Woodley, D. Nck/Dock: an adapter between cell surface receptors and the actin cytoskeleton. Oncogene 20, 6403–6417 (2001). https://doi.org/10.1038/sj.onc.1204782

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204782

Keywords

This article is cited by

Search

Quick links