This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cooper, L. A.
Right arrow Articles by Guan, J.-L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cooper, L. A.
Right arrow Articles by Guan, J.-L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2003, p. 8030-8041, Vol. 23, No. 22
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.22.8030-8041.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Regulation of Focal Adhesion Kinase by Its Amino-Terminal Domain through an Autoinhibitory Interaction

Lee Ann Cooper, Tang-Long Shen, and Jun-Lin Guan*

Department of Molecular Medicine, Cornell University, Ithaca, New York 14853

Received 19 February 2003/ Returned for modification 28 April 2003/ Accepted 16 August 2003

We have investigated a role for the amino-terminal FERM-like domain of the focal adhesion kinase (FAK) as a negative regulator of its own activity and phosphorylation state. Deletion of the first 375 amino acids from the amino terminus of FAK increases its catalytic activity in vitro, its phosphorylation when expressed in mammalian cells, and the phosphorylation of a FAK substrate, paxillin. Deletion mutants are phosphorylated in suspension, suggesting that they are no longer regulated by adhesion. The amino terminus of FAK can interact with the kinase domain of FAK in vitro and in vivo, suggesting that it might act as an autoinhibitor of FAK activity. The amino terminus of FAK can act in trans to inhibit FAK phosphorylation when expressed in mammalian cells or to directly inhibit FAK activity in vitro. Expression of the amino terminus of FAK inhibits cell cycle progression in CHO cells, consistent with its inhibition of FAK phosphorylation and function in trans. A glutathione S-transferase fusion protein containing the cytoplasmic tail of the ß1 integrin stimulates FAK activity in vitro, suggesting that FAK could be regulated by molecular interactions with the amino terminus. Based on these and previous data, we propose a working model for activation of FAK in cell adhesion.

* Corresponding author. Mailing address: Department of Molecular Medicine, Cornell University, Ithaca, NY 14853. Phone: (607) 253-3586. Fax: (607) 253-3708. E-mail: jg19{at}cornell.edu.

Molecular and Cellular Biology, November 2003, p. 8030-8041, Vol. 23, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.22.8030-8041.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Park, A. Y. J., Shen, T.-L., Chien, S., Guan, J.-L. (2009). Role of Focal Adhesion Kinase Ser-732 Phosphorylation in Centrosome Function during Mitosis. J. Biol. Chem. 284: 9418-9425 [Abstract] [Full Text]  
  • Papusheva, E., de Queiroz, F. M., Dalous, J., Han, Y., Esposito, A., Jares-Erijmanxa, E. A., Jovin, T. M., Bunt, G. (2009). Dynamic conformational changes in the FERM domain of FAK are involved in focal-adhesion behavior during cell spreading and motility. J. Cell Sci. 122: 656-666 [Abstract] [Full Text]  
  • Piao, Y., Lu, L., de Groot, J. (2009). AMPA receptors promote perivascular glioma invasion via {beta}1 integrin-dependent adhesion to the extracellular matrix. Neuro Oncol Duke 11: 260-273 [Abstract] [Full Text]  
  • Wei, W.-C., Lin, H.-H., Shen, M.-R., Tang, M.-J. (2008). Mechanosensing machinery for cells under low substratum rigidity. Am. J. Physiol. Cell Physiol. 295: C1579-C1589 [Abstract] [Full Text]  
  • Carlucci, A., Gedressi, C., Lignitto, L., Nezi, L., Villa-Moruzzi, E., Avvedimento, E. V., Gottesman, M., Garbi, C., Feliciello, A. (2008). Protein-tyrosine Phosphatase PTPD1 Regulates Focal Adhesion Kinase Autophosphorylation and Cell Migration. J. Biol. Chem. 283: 10919-10929 [Abstract] [Full Text]  
  • Cai, X., Lietha, D., Ceccarelli, D. F., Karginov, A. V., Rajfur, Z., Jacobson, K., Hahn, K. M., Eck, M. J., Schaller, M. D. (2008). Spatial and Temporal Regulation of Focal Adhesion Kinase Activity in Living Cells. Mol. Cell. Biol. 28: 201-214 [Abstract] [Full Text]  
  • Schlaepfer, D. D., Hou, S., Lim, S.-T., Tomar, A., Yu, H., Lim, Y., Hanson, D. A., Uryu, S. A., Molina, J., Mitra, S. K. (2007). Tumor Necrosis Factor-{alpha} Stimulates Focal Adhesion Kinase Activity Required for Mitogen-activated Kinase-associated Interleukin 6 Expression. J. Biol. Chem. 282: 17450-17459 [Abstract] [Full Text]  
  • Lim, Y., Park, H., Jeon, J., Han, I., Kim, J., Jho, E.-H., Oh, E.-S. (2007). Focal Adhesion Kinase Is Negatively Regulated by Phosphorylation at Tyrosine 407. J. Biol. Chem. 282: 10398-10404 [Abstract] [Full Text]  
  • Gan, B., Yoo, Y., Guan, J.-L. (2006). Association of Focal Adhesion Kinase with Tuberous Sclerosis Complex 2 in the Regulation of S6 Kinase Activation and Cell Growth. J. Biol. Chem. 281: 37321-37329 [Abstract] [Full Text]  
  • Chen, S.-Y., Chen, H.-C. (2006). Direct Interaction of Focal Adhesion Kinase (FAK) with Met Is Required for FAK To Promote Hepatocyte Growth Factor-Induced Cell Invasion.. Mol. Cell. Biol. 26: 5155-5167 [Abstract] [Full Text]  
  • Siesser, P. M.F., Hanks, S. K. (2006). The Signaling and Biological Implications of FAK Overexpression in Cancer.. Clin. Cancer Res. 12: 3233-3237 [Full Text]  
  • Ceccarelli, D. F. J., Song, H. K., Poy, F., Schaller, M. D., Eck, M. J. (2006). Crystal Structure of the FERM Domain of Focal Adhesion Kinase. J. Biol. Chem. 281: 252-259 [Abstract] [Full Text]  
  • Li, W., Aurandt, J., Jurgensen, C., Rao, Y., Guan, K.-L. (2006). FAK and Src kinases are required for netrin-induced tyrosine phosphorylation of UNC5. J. Cell Sci. 119: 47-55 [Abstract] [Full Text]  
  • Samarel, A. M. (2005). Costameres, focal adhesions, and cardiomyocyte mechanotransduction. Am. J. Physiol. Heart Circ. Physiol. 289: H2291-H2301 [Abstract] [Full Text]  
  • Usatyuk, P. V., Natarajan, V. (2005). Regulation of reactive oxygen species-induced endothelial cell-cell and cell-matrix contacts by focal adhesion kinase and adherens junction proteins. Am. J. Physiol. Lung Cell. Mol. Physiol. 289: L999-L1010 [Abstract] [Full Text]  
  • Grigera, P. R., Jeffery, E. D., Martin, K. H., Shabanowitz, J., Hunt, D. F., Parsons, J. T. (2005). FAK phosphorylation sites mapped by mass spectrometry. J. Cell Sci. 118: 4931-4935 [Full Text]  
  • Cohen, L. A., Guan, J.-L. (2005). Residues within the First Subdomain of the FERM-like Domain in Focal Adhesion Kinase Are Important in Its Regulation. J. Biol. Chem. 280: 8197-8207 [Abstract] [Full Text]  
  • Fonseca, P. M., Inoue, R. Y., Kobarg, C. B., Crosara-Alberto, D. P., Kobarg, J., Franchini, K. G. (2005). Targeting to C-Terminal Myosin Heavy Chain May Explain Mechanotransduction Involving Focal Adhesion Kinase in Cardiac Myocytes. Circ. Res. 96: 73-81 [Abstract] [Full Text]  
  • Grabbe, C., Zervas, C. G., Hunter, T., Brown, N. H., Palmer, R. H. (2004). Focal adhesion kinase is not required for integrin function or viability in Drosophila. Development 131: 5795-5805 [Abstract] [Full Text]  
  • Dunty, J. M., Gabarra-Niecko, V., King, M. L., Ceccarelli, D. F. J., Eck, M. J., Schaller, M. D. (2004). FERM Domain Interaction Promotes FAK Signaling. Mol. Cell. Biol. 24: 5353-5368 [Abstract] [Full Text]  
  • Wu, X., Suetsugu, S., Cooper, L. A., Takenawa, T., Guan, J.-L. (2004). Focal Adhesion Kinase Regulation of N-WASP Subcellular Localization and Function. J. Biol. Chem. 279: 9565-9576 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»