This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barazi, H. O. Articles by Roberts, D. D. Search for Related Content PubMed PubMed Citation Articles by Barazi, H. O. Articles by Roberts, D. D.

Identification of Heat Shock Protein 60 as a Molecular Mediator of 3ß1 Integrin Activation

Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892 [H. O. B., L. Z., H. C. K., D. D. R.], and Center for Cell and Gene Therapy and Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas 77030 [N. S. T.]

The 3ß1 integrin is involved in the adhesion of metastatic breast cancer cells to the lymph nodes and to osteoblasts in the bone. Regulation of the affinity or avidity of integrins for their ligands may result from conformational changes induced by changes in the microenvironment of the integrin. Two surface proteins, 55 and 32 kDa, coimmunoprecipitated with the 3ß1 integrin from breast carcinoma cells. The 55-kDa protein preferentially associated with the active form of the 3ß1 integrin. The protein was identified as HSP60 using two-dimensional electrophoresis and mass spectrometry and confirmed by reimmunoprecipitation of the integrin immune complex with an anti-HSP60 antibody. In cell spreading assays on a thrombospondin-1 substrate, addition of exogenous-recombinant HSP60 was sufficient to specifically activate 3ß1 integrin but not to activate function of 2ß1, vß3, 4ß1, or 5ß1 integrins. Furthermore, mizoribine, an HSP60-binding drug, blocked activation of the 3ß1 integrin induced by insulin-like growth factor 1 (IGF1) or exogenous recombinant HSP60 and inhibited the association of HSP60 with the integrin. Additionally, inhibiting the surface expression of endogenous HSP60 by nonactin inhibited activation of the 3ß1 integrin by IGF1. These data demonstrate that HSP60 binding is sufficient to activate 3ß1 integrin function and suggest that association of endogenous HSP60 with 3ß1 integrin is necessary for IGF1-induced activation.

This article has been cited by other articles:

				Y.-P. Tsai, M.-H. Yang, C.-H. Huang, S.-Y. Chang, P.-M. Chen, C.-J. Liu, S.-C. Teng, and K.-J. Wu Interaction between HSP60 and {beta}-catenin promotes metastasis Carcinogenesis, June 1, 2009; 30(6): 1049 - 1057. [Abstract] [Full Text] [PDF]

				A. Walsh, D. Whelan, A. Bielanowicz, B. Skinner, R. J. Aitken, M. K. O'Bryan, and B. Nixon Identification of the Molecular Chaperone, Heat Shock Protein 1 (Chaperonin 10), in the Reproductive Tract and in Capacitating Spermatozoa in the Male Mouse Biol Reprod, June 1, 2008; 78(6): 983 - 993. [Abstract] [Full Text] [PDF]

				M. W. Graner and D. D. Bigner Chaperone proteins and brain tumors: Potential targets and possible therapeutics Neuro-oncol, July 1, 2005; 7(3): 260 - 278. [Abstract] [PDF]

				G. Pfister, C. M. Stroh, H. Perschinka, M. Kind, M. Knoflach, P. Hinterdorfer, and G. Wick Detection of HSP60 on the membrane surface of stressed human endothelial cells by atomic force and confocal microscopy J. Cell Sci., April 15, 2005; 118(8): 1587 - 1594. [Abstract] [Full Text] [PDF]

				B. J. Johnson, T. T. T. Le, C. A. Dobbin, T. Banovic, C. B. Howard, F. d. M. L. Flores, D. Vanags, D. J. Naylor, G. R. Hill, and A. Suhrbier Heat Shock Protein 10 Inhibits Lipopolysaccharide-induced Inflammatory Mediator Production J. Biol. Chem., February 11, 2005; 280(6): 4037 - 4047. [Abstract] [Full Text] [PDF]

				M. J. Calzada, D. S. Annis, B. Zeng, C. Marcinkiewicz, B. Banas, J. Lawler, D. F. Mosher, and D. D. Roberts Identification of Novel {beta}1 Integrin Binding Sites in the Type 1 and Type 2 Repeats of Thrombospondin-1 J. Biol. Chem., October 1, 2004; 279(40): 41734 - 41743. [Abstract] [Full Text] [PDF]

				J. L. Wampler, K.-P. Kim, Z. Jaradat, and A. K. Bhunia Heat Shock Protein 60 Acts as a Receptor for the Listeria Adhesion Protein in Caco-2 Cells Infect. Immun., February 1, 2004; 72(2): 931 - 936. [Abstract] [Full Text] [PDF]

				Y.-x. Shan, T.-L. Yang, R. Mestril, and P. H. Wang Hsp10 and Hsp60 Suppress Ubiquitination of Insulin-like Growth Factor-1 Receptor and Augment Insulin-like Growth Factor-1 Receptor Signaling in Cardiac Muscle: IMPLICATIONS ON DECREASED MYOCARDIAL PROTECTION IN DIABETIC CARDIOMYOPATHY J. Biol. Chem., November 14, 2003; 278(46): 45492 - 45498. [Abstract] [Full Text] [PDF]

				D. R. Clemmons and L. A. Maile Minireview: Integral Membrane Proteins that Function Coordinately with the Insulin-Like Growth Factor I Receptor to Regulate Intracellular Signaling Endocrinology, May 1, 2003; 144(5): 1664 - 1670. [Abstract] [Full Text] [PDF]

				B. Billack, D. E. Heck, T. M. Mariano, C. R. Gardner, R. Sur, D. L. Laskin, and J. D. Laskin Induction of cyclooxygenase-2 by heat shock protein 60 in macrophages and endothelial cells Am J Physiol Cell Physiol, October 1, 2002; 283(4): C1267 - C1277. [Abstract] [Full Text] [PDF]

				D. G. Stupack and D. A. Cheresh Get a ligand, get a life: integrins, signaling and cell survival J. Cell Sci., January 10, 2002; 115(19): 3729 - 3738. [Abstract] [Full Text] [PDF]