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.

  • Original Paper
  • Published:

Identification of a novel interaction between integrin β1 and 14-3-3β

Oncogene volume 20, pages 346–357 (2001)Cite this article

Abstract

Integrins are cell surface receptors for extracellular matrix, which play important roles in a variety of biological processes. 14-3-3 proteins are a highly conserved family of cytoplasmic proteins that associate with several intracellular signaling molecules in regulation of various cellular functions. Here, we report identification of an interaction between the integrin β1 cytoplasmic domain and 14-3-3β by using the yeast two-hybrid screen. Like several other proteins, the integrin β1 cytoplasmic domain associated with 14-3-3β by a non-phosphoserine mechanism. The 14-3-3β/integrin β1 interaction was confirmed by in vitro binding assays as well as co-precipitation in vivo. Furthermore, we found that 14-3-3β co-localized with integrin β1 during the early stage of cell spreading on fibronectin, suggesting a potential role of the 14-3-3β/integrin β1 interaction in the regulation of cell adhesion. Using tetracycline-regulated expression system, we showed that overexpression of 14-3-3β stimulated cell spreading and migration on fibronectin but not on poly-L-lysine. However, the induced expression of 14-3-3β did not affect tyrosine phosphorylation of FAK or its substrates, p130cas and paxillin, suggesting that 14-3-3β regulated integrin-mediated cell spreading and migration by FAK-independent mechanisms. Taken together, these results identify an interaction between integrin and 14-3-3 proteins and suggest a potentially novel cellular function for 14-3-3 proteins in the regulation of integrin-mediated cell adhesion and signaling events.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

Abbreviations

ECM:

extracellular matrix

PLL:

poly-L-lysine

FN:

human plasma fibronectin

DMEM:

Dulbecco's modified Eagle's medium

FBS:

fetal bovine serum

CS:

calf serum

References

  • Aitken A, Jones D, Soneji Y and Howell S. . 1995 Biochem. Soc. Trans. 23: 605–611.

  • Akiyama SK, Yamada SS, Yamada KM and LaFlamme SE. . 1994 J. Biol. Chem. 269: 15961–15964.

  • Aplin AE, Howe A, Alahari SK and Juliano RL. . 1998 Pharmacol. Rev. 50: 197–263.

  • Autieri MV, Haines DS, Romanic AM and Ohlstein EH. . 1996 Cell Growth Differ. 7: 1453–1460.

  • Bonnefoy-Berard N, Liu YC, von Willebrand M, Sung A, Elly C, Mustelin T, Yoshida H, Ishizaka K and Altman A. . 1995 Proc. Natl. Acad. Sci. USA 92: 10142–10146.

  • Braselmann S and McCormick F. . 1995 EMBO J. 14: 4839–4848.

  • Cary LA, Chang JF and Guan JL. . 1996 J. Cell. Sci. 109: 1787–1794.

  • Cary LA, Han DC, Polte TR, Hanks SK and Guan JL. . 1998 J. Cell. Biol. 140: 211–221.

  • Chang DD, Wong C, Smith H and Liu J. . 1997 J. Cell. Biol. 138: 1149–1157.

  • Chen HC and Guan JL. . 1994 Proc. Natl. Acad. Sci. USA 91: 10148–10152.

  • Chun JS and Jacobson BS. . 1993 Mol. Biol. Cell. 4: 271–281.

  • Clark EA and Brugge JS. . 1995 Science 268: 233–239.

  • Clark GJ, Drugan JK, Rossman KL, Carpenter JW, Rogers-Graham K, Fu H, Der CJ and Campbell SL. . 1997 J. Biol. Chem. 272: 20990–20993.

  • Conklin DS, Galaktionov K and Beach D. . 1995 Proc. Natl. Acad. Sci. USA 92: 7892–7896.

  • Craparo A, Freund R and Gustafson TA. . 1997 J. Biol. Chem. 272: 11663–11669.

  • Fantl WJ, Muslin AJ, Kikuchi A, Martin JA, MacNicol AM, Gross RW and Williams LT. . 1994 Nature 371: 612–614.

  • Freed E, Symons M, Macdonald SG, McCormick F and Ruggieri R. . 1994 Science 265: 1713–1716.

  • Fu H, Subramanian RR and Masters SC. . 2000 Annu. Rev. Pharmacol. Toxicol. 40: 617–647.

  • Fu H, Xia K, Pallas DC, Cui C, Conroy K, Narsimhan RP, Mamon H, Collier RJ and Roberts TM. . 1994 Science 266: 126–129.

  • Garcia-Guzman M, Dolfi F, Russello M and Vuori K. . 1999 J. Biol. Chem. 274: 5762–5768.

  • Gilmore AP and Romer LH. . 1996 Mol. Biol. Cell. 7: 1209–1224.

  • Guan JL, Trevithick JE and Hynes RO. . 1991 Cell Regul. 2: 951–964.

  • Han DC and Guan JL. . 1999 J. Biol. Chem. 274: 24425–24430.

  • Hannigan GE, Leung-Hagesteijn C, Fitz-Gibbon L, Coppolino MG, Radeva G, Filmus J, Bell JC and Dedhar S. . 1996 Nature 379: 91–96.

  • Hannon GJ, Demetrick D and Beach D. . 1993 Genes Dev. 7: 2378–2391.

  • Hausser A, Storz P, Link G, Stoll H, Liu YC, Altman A, Pfizenmaier K and Johannes FJ. . 1999 J. Biol. Chem. 274: 9258–9264.

  • Horwitz A, Duggan K, Buck C, Beckerle MC and Burridge K. . 1986 Nature 320: 531–533.

  • Hughes PE, Diaz-Gonzalez F, Leong L, Wu C, McDonald JA, Shattil SJ and Ginsberg MH. . 1996 J. Biol. Chem. 271: 6571–6574.

  • Hynes RO. . 1992 Cell 69: 11–25.

  • Ilic D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N, Nomura S, Fujimoto J, Okada M and Yamamoto T. . 1995 Nature 377: 539–544.

  • Irie K, Gotoh Y, Yashar BM, Errede B, Nishida E and Matsumoto K. . 1994 Science 265: 1716–1719.

  • Khwaja A, Rodriguez-Viciana P, Wennstrom S, Warne PH and Downward J. . 1997 EMBO J. 16: 2783–2793.

  • Klemke RL, Leng J, Molander R, Brooks PC, Vuori K and Cheresh DA. . 1998 J. Cell. Biol. 140: 961–972.

  • Kolanus W, Nagel W, Schiller B, Zeitlmann L, Godar S, Stockinger H and Seed B. . 1996 Cell 86: 233–242.

  • LaFlamme SE, Akiyama SK and Yamada KM. . 1992 J. Cell. Biol. 117: 437–447.

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

  • Lin TH, Aplin AE, Shen Y, Chen Q, Schaller M, Romer L, Aukhil I and Juliano RL. . 1997 J. Cell. Biol. 136: 1385–1395.

  • Liu YC, Liu Y, Elly C, Yoshida H, Lipkowitz S and Altman A. . 1997 J. Biol. Chem. 272: 9979–9985.

  • Loftus JC and Liddington RC. . 1997 J. Clin. Invest. 100: S77–S81.

  • Loo DT, Kanner SB and Aruffo A. . 1998 J. Biol. Chem. 273: 23304–23312.

  • Marcantonio EE, Guan JL, Trevithick JE and Hynes RO. . 1990 Cell Regul. 1: 597–604.

  • Marcantonio EE and Hynes RO. . 1988 J. Cell. Biol. 106: 1765–1772.

  • Masters SC, Pederson KJ, Zhang L, Barbieri JT and Fu H. . 1999 Biochemistry 38: 5216–5221.

  • Meller N, Liu YC, Collins TL, Bonnefoy-Berard N, Baier G, Isakov N and Altman A. . 1996 Mol. Cell. Biol. 16: 5782–5791.

  • Miranti CK, Ohno S and Brugge JS. . 1999 J. Biol. Chem. 274: 10571–10581.

  • Miyamoto S, Teramoto H, Coso OA, Gutkind JS, Burbelo PD, Akiyama SK and Yamada KM. . 1995 J. Cell. Biol. 131: 791–805.

  • Morgan A and Burgoyne RD. . 1992 Biochem. J. 286: 807–811.

  • Muslin AJ, Tanner JW, Allen PM and Shaw AS. . 1996 Cell 84: 889–897.

  • Nakanishi K, Hashizume S, Kato M, Honjoh T, Setoguchi Y and Yasumoto K. . 1997 Hum. Antibodies 8: 189–194.

  • O'Toole TE, Katagiri Y, Faull RJ, Peter K, Tamura R, Quaranta V, Loftus JC, Shattil SJ and Ginsberg MH. . 1994 J. Cell. Biol. 124: 1047–1059.

  • O'Toole TE, Loftus JC, Du XP, Glass AA, Ruggeri ZM, Shattil SJ, Plow EF and Ginsberg MH. . 1990 Cell Regul. 1: 883–893.

  • Otey CA, Pavalko FM and Burridge K. . 1990 J. Cell. Biol. 111: 721–729.

  • Pasqualini R and Hemler ME. . 1994 J. Cell. Biol. 125: 447–460.

  • Pfaff M, Liu S, Erle DJ and Ginsberg MH. . 1998 J. Biol. Chem. 273: 6104–6109.

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

  • Reuther GW, Fu H, Cripe LD, Collier RJ and Pendergast AM. . 1994 Science 266: 129–133.

  • Richardson A and Parsons T. . 1996 Nature 380: 538–540.

  • Schaller MD, Otey CA, Hildebrand JD and Parsons JT. . 1995 J. Cell. Biol. 130: 1181–1187.

  • Schwartz MA, Schaller MD and Ginsberg MH. . 1995 Annu. Rev. Cell. Dev. Biol. 11: 549–599.

  • Sharma CP, Ezzell RM and Arnaout MA. . 1995 J. Immunol. 154: 3461–3470.

  • Shattil SJ, Kashiwagi H and Pampori N. . 1998 Blood 91: 2645–2657.

  • Shattil SJ, O'Toole T, Eigenthaler M, Thon V, Williams M, Babior BM and Ginsberg MH. . 1995 J. Cell. Biol. 131: 807–816.

  • Solowska J, Guan JL, Marcantonio EE, Trevithick JE, Buck CA and Hynes RO. . 1989 J. Cell. Biol. 109: 853–861.

  • Tahiliani PD, Singh L, Auer KL and LaFlamme SE. . 1997 J. Biol. Chem. 272: 7892–7898.

  • Toker A, Sellers LA, Amess B, Patel Y, Harris A and Aitken A. . 1992 Eur. J. Biochem. 206: 453–461.

  • Villaret DB, Wang T, Dillon D, Xu J, Sivam D, Cheever MA and Reed SG. . 2000 Laryngoscope 110: 374–381.

  • Vuori K and Ruoslahti E. . 1993 J. Biol. Chem. 268: 21459–21462.

  • Wang B, Yang H, Liu YC, Jelinek T, Zhang L, Ruoslahti E and Fu H. . 1999 Biochemistry 38: 12499–12504.

  • Wu C, Keivens VM, O'Toole TE, McDonald JA and Ginsberg MH. . 1995 Cell 83: 715–724.

  • Xing Z, Chen HC, Nowlen JK, Taylor SJ, Shalloway D and Guan JL. . 1994 Mol. Biol. Cell. 5: 413–421.

  • Yaffe MB, Rittinger K, Volinia S, Caron PR, Aitken A, Leffers H, Gamblin SJ, Smerdon SJ and Cantley LC. . 1997 Cell 91: 961–971.

  • Zhang L, Chen J and Fu H. . 1999 Proc. Natl. Acad. Sci. USA 96: 8511–8515.

  • Zhang SH, Kobayashi R, Graves PR, Piwnica-Worms H and Tonks NK. . 1997 J. Biol. Chem. 272: 27281–27287.

  • Zhang XA and Hemler ME. . 1999 J. Biol. Chem. 274: 11–19.

  • Zhao JH, Reiske H and Guan JL. . 1998 J. Cell. Biol. 143: 1997–2008.

Download references

Acknowledgements

We are grateful to Dr Kevin Struhl of Harvard medical school for plasmid pLEX-GCN4, Dr Xiao-Ping Du of University of Illinois at Chicago for human integrin β3 cDNA, Dr G Hannon of Cold Spring Harbor Laboratory for HeLa cell cDNA library, and Dr Sandy Shattil of Scripps Research Institute for plasmid pGAD-β3-endonexin. We thank Ji He Zhao, Hiroki Ueda, Renee Christopher, Heinz Reiske, Smita Abbi and Tang-Long Shen for their critical reading of the manuscript and helpful comments. This research was supported by NIH grants GM48050 to J-L Guan. J-L Guan is an Established Investigator of the American Heart Association.

Author information

Authors and Affiliations

  1. Department of Molecular Medicine, Cancer Biology Laboratories, College of Veterinary Medicine, Cornell University, Ithaca, 14853, New York, NY, USA

    Dong Cho Han, Luis G Rodriguez & Jun-Lin Guan

Authors
  1. Dong Cho Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luis G Rodriguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jun-Lin Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Han, D., Rodriguez, L. & Guan, JL. Identification of a novel interaction between integrin β1 and 14-3-3β. Oncogene 20, 346–357 (2001). https://doi.org/10.1038/sj.onc.1204068

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204068

Keywords

This article is cited by

Search

Advanced search

Quick links