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:

The actin filament-associated protein AFAP-110 is an adaptor protein that modulates changes in actin filament integrity

Abstract

The actin filament-associated protein of 110 kDa (AFAP-110) was first identified as an SH3/SH2 binding partner for the nonreceptor tyrosine kinase, Src. Subsequent data have demonstrated that AFAP-110 can interact with other Src family members. AFAP-110 contains additional protein binding modules including two pleckstrin homology domains, a leucine zipper motif and a target sequence for serine/threonine phosphorylation. AFAP-110 interacts with actin filaments directly via a carboxy terminal actin-binding domain. Thus AFAP-110 may function as an adaptor protein by linking Src family members and/or other signaling proteins to actin filaments. AFAP-110 also has an intrinsic capability to alter actin filament integrity that can be revealed upon conformational changes associated with phosphorylation or mutagenesis. Recent data has indicated that AFAP-110 may also serve to activate cSrc in response to this conformational change as well. Thus, AFAP-110 may function in several ways by (1) acting as an adaptor protein that links signaling molecules to actin filaments, (2) serving as a platform for the construction of larger signaling complexes, (3) serving as an activator of Src family kinases in response to cellular signals that alter its conformation and (4) directly effecting actin filament organization as an actin filament cross-linking protein. Here, we will review the structure and function of AFAP-110 as well as potential binding partners and effectors of AFAP-110's ability to alter actin filament integrity.

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
Figure 5

Similar content being viewed by others

References

  • Alonso G, Koegl M, Mazurenko N, Courtneidge SA . 1995 J. Biol. Chem. 270: 9840–9848

  • Baraldi E, Carugo KD, Hyvonen M, Surdo PL, Riley AM, Potter BV, O'Brien R, Ladbury JE, Saraste M . 1999 Structure. Fold. Des 7: 449–460

  • Briggs SD, Sharkey M, Stevenson M, Smithgall TE . 1997 J. Biol. Chem. 272: 17899–17902

  • Brown MT, Cooper JA . 1996 Biochim. Biophys. Acta 1287: 121–149

  • Bubb MR, Lenox RH, Edison AS . 1999 J. Biol. Chem. 274: 36472–36478

  • Cartwright CA, Meisler AI, Eckhart W . 1990 Proc. Natl. Acad. Sci. USA 87: 558–562

  • Cramer LP . 1997 Front Biosci. 2: d260–d270

  • Davis S, Lu ML, Lo SH, Lin S, Butler JA, Druker BJ, Roberts TM, An Q, Chen LB . 1991 Science 252: 712–715

  • Dwyer-Nield LD, Miller AC, Neighbors BW, Dinsdale D, Malkinson AM . 1996 Am. J. Physiol 270: L526–L534

  • Fechheimer M, Zigmond SH . 1993 J. Cell Biol. 123: 1–5

  • Felice GR, Eason P, Nermut MV, Kellie S . 1990 Eur. J. Cell Biol. 52: 47–59

  • Fincham VJ, Brunton VG, Frame MC . 2000 Mol. Cell Biol. 20: 6518–6536

  • Fincham VJ, Chudleigh A, Frame MC . 1999 J. Cell Sci. 112: 947–956

  • Flynn DC, Koay TC, Humphries CG, Guappone AC . 1995 J. Biol. Chem. 270: 3894–3899

  • Flynn DC, Leu TH, Reynolds AB, Parsons JT . 1993 Mol. Cell Biol. 13: 7892–7900

  • Flynn DC, Schaller MD, Parsons JT . 1992 Oncogene 7: 579–583

  • Fukui Y, O'Brien MC, Hanafusa H . 1991 Mol. Cell Biol. 11: 1207–1213

  • Fukuoka M, Suetsugu S, Miki H, Fukami K, Endo T, Takenawa T . 2001 J. Cell Biol. 152: 471–482

  • Gibson TJ, Hyvonen M, Musacchio A, Saraste M, Birney E . 1994 Trends Biochem. Sci. 19: 349–353

  • Gray A, Van Der KJ, Downes CP . 1999 Biochem. J. 344: 929–936

  • Guappone AC, Flynn DC . 1997 Mol. Cell Biochem. 175: 243–252

  • Guappone AC, Weimer T, Flynn DC . 1998 Mol. Carcinog. 22: 110–119

  • Harbeck B, Huttelmaier S, Schluter K, Jockusch BM, Illenberger S . 2000 J. Biol. Chem. 275: 30817–30825

  • Harte MT, Hildebrand JD, Burnham MR, Bouton AH, Parsons JT . 1996 J. Biol. Chem. 271: 13649–13655

  • Hartwig JH, Thelen M, Rosen A, Janmey PA, Nairn AC, Aderem A . 1992 Nature 356: 618–622

  • Hodges RS . 1996 Biochem. Cell Biol. 74: 133–154

  • Huang C, Ni Y, Wang T, Gao Y, Haudenschild CC, Zhan X . 1997 J. Biol. Chem. 272: 13911–13915

  • Hyvonen M, Macias MJ, Nilges M, Oschkinat H, Saraste M, Wilmanns M . 1995 EMBO J. 14: 4676–4685

  • Ishikawa R, Yamashiro S, Kohama K, Matsumura F . 1998 J. Biol. Chem. 273: 26991–26997

  • Kanner SB, Reynolds AB, Vines RR, Parsons JT . 1990 Proc. Natl. Acad. Sci. USA 87: 3328–3332

  • Kanner SB, Reynolds AB, Wang HC, Vines RR, Parsons JT . 1991 EMBO J. 10: 1689–1698

  • Keshavjee S, Zhang XM, Fischer S, Liu M . 2000 Transplantation 70: 525–531

  • Kojima T, Fukuda M, Watanabe Y, Hamazato F, Mikoshiba K . 1997 Biochem. Biophys. Res. Commun. 236: 333–339

  • Kouzarides T, Ziff E . 1988 Nature 336: 646–651

  • Lemmon MA, Ferguson KM . 2000 Biochem. J. 350: 1–18

  • Lemmon MA, Ferguson KM, O'Brien R, Sigler PB, Schlessinger J . 1995 Proc. Natl. Acad. Sci. USA 92: 10472–10476

  • Liu M, Qin Y, Liu J, Tanswell AK, Post M . 1996 J. Biol. Chem. 271: 7066–7071

  • Liu X, Brodeur SR, Gish G, Songyang Z, Cantley LC, Laudano AP, Pawson T . 1993 Oncogene 8: 1119–1126

  • Macias MJ, Musacchio A, Ponstingl H, Nilges M, Saraste M, Oschkinat H . 1994 Nature 369: 675–677

  • Matsudaira P . 1991 Trends Biochem. Sci. 16: 87–92

  • Moarefi I, LaFevre-Bernt M, Sicheri F, Huse M, Lee CH, Kuriyan J, Miller WT . 1997 Nature 385: 650–653

  • Morris GE, Sedgwick SG, Ellis JM, Pereboev A, Chamberlain JS, Nguyen tM . 1998 Biochemistry 37: 11117–11127

  • Murray RC, Calof AL . 1999 Semin. Cell Dev. Biol. 10: 421–431

  • Nemoto T, Ohara-Nemoto Y, Ota M, Takagi T, Yokoyama K . 1995 Eur. J. Biochem. 233: 1–8

  • Oldenbourg R, Katoh K, Danuser G . 2000 Biophys. J. 78: 1176–1182

  • Pawson T . 1995 Nature 373: 573–580

  • Pollard TD, Cooper JA . 1986 Annu. Rev. Biochem. 55: 987–1035

  • Qian Y, Baisden JM, Westin EH, Guappone AC, Koay TC, Flynn DC . 1998 Oncogene 16: 2185–2195

  • Qian Y, Baisden JM, Zot HG, Van Winkle WB, Flynn DC . 2000 Exp. Cell Res. 255: 102–113

  • Qian Y, Guappone AC, Baisden JM, Hill MW, Summy JM, Flynn DC . 1999 Hybridoma 18: 167–175

  • Ren R, Mayer BJ, Cicchetti P, Baltimore D . 1993 Science 259: 1157–1161

  • Reynolds AB, Daniel J, McCrea PD, Wheelock MJ, Wu J, Zhang Z . 1994 Mol. Cell Biol. 14: 8333–8342

  • Reynolds AB, Kanner SB, Wang HC, Parsons JT . 1989a Mol. Cell Biol. 9: 3951–3958

  • Reynolds AB, Roesel DJ, Kanner SB, Parsons JT . 1989b Mol. Cell Biol. 9: 629–638

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

  • Rosen N, Bolen JB, Schwartz AM, Cohen P, DeSeau V, Israel MA . 1986 J. Biol. Chem. 261: 13754–13759

  • Schaller MD, Borgman CA, Cobb BS, Vines RR, Reynolds AB, Parsons JT . 1992 Proc. Natl. Acad. Sci. USA 89: 5192–5196

  • Scholler JK, Kanner SB . 1997 DNA Cell Biol. 16: 515–531

  • Seidel-Dugan C, Meyer BE, Thomas SM, Brugge JS . 1992 Mol. Cell Biol. 12: 1835–1845

  • Shaw G . 1996 Bioessays 18: 35–46

  • Shiraishi Y, Mizutani A, Bito H, Fujisawa K, Narumiya S, Mikoshiba K, Furuichi T . 1999 J. Neurosci. 19: 8389–8400

  • Small JV . 1994 Semin. Cell Biol. 5: 157–163

  • Songyang Z, Shoelson SE, Chaudhuri M, Gish G, Pawson T, Haser WG, King F, Roberts T, Ratnofsky S, Lechleider RJ, Neel BG, Birge RB, Fajardo JE, Chou MM, Hanafusa H, Schaffhausen B, Cantley LC . 1993 Cell 72: 767–778

  • Summy JM, Guappone AC, Sudol M, Flynn DC . 2000 Oncogene 19: 155–160

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

  • Verkhusha VV, Tsukita S, Oda H . 1999 FEBS Lett. 445: 395–401

  • Wachsstock DH, Schwartz WH, Pollard TD . 1993 Biophys. J. 65: 205–214

  • Waldron RT, Iglesias T, Rozengurt E . 1999 J. Biol. Chem. 274: 9224–9230

  • Weng Z, Rickles RJ, Feng S, Richard S, Shaw AS, Schreiber SL, Brugge JS . 1995 Mol. Cell Biol. 15: 5627–5634

  • Williams JC, Weijland A, Gonfloni S, Thompson A, Courtneidge SA, Superti-Furga G, Wierenga RK . 1997 J. Mol. Biol. 274: 757–775

  • Wu H, Reynolds AB, Kanner SB, Vines RR, Parsons JT . 1991 Mol. Cell Biol. 11: 5113–5124

  • Xu J, Wirtz D, Pollard TD . 1998 J. Biol. Chem. 273: 9570–9576

  • Yagi T, Aizawa S, Tokunaga T, Shigetani Y, Takeda N, Ikawa Y . 1993 Nature 366: 742–745

  • Yamakita Y, Ono S, Matsumura F, Yamashiro S . 1996 J. Biol. Chem. 271: 12632–12638

  • Yao L, Kawakami Y, Kawakami T . 1994 Proc. Natl. Acad. Sci. USA 91: 9175–9179

  • Yao L, Suzuki H, Ozawa K, Deng J, Lehel C, Fukamachi H, Anderson WB, Kawakami Y, Kawakami T . 1997 J. Biol. Chem. 272: 13033–13039

Download references

Acknowledgements

The authors would like to acknowledge Michael Seckl, Bing-Hua Jiang, Mingyao Liu, Sue Fessler and Jamie Enomoto-Baisden for critical review and comments. This work was supported by a grant from the NCI, CA60731.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Daniel C Flynn.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baisden, J., Qian, Y., Zot, H. et al. The actin filament-associated protein AFAP-110 is an adaptor protein that modulates changes in actin filament integrity. Oncogene 20, 6435–6447 (2001). https://doi.org/10.1038/sj.onc.1204784

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204784

Keywords

This article is cited by

Search

Quick links