HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Bazzoni, G. Articles by Hemler, M. E. Search for Related Content PubMed PubMed Citation Articles by Bazzoni, G. Articles by Hemler, M. E. Social Bookmarking                      What's this?

J Biol Chem, Vol. 273, Issue 12, 6670-6678, March 20, 1998

Divalent Cations and Ligands Induce Conformational Changes That Are Highly Divergent among ₁ Integrins

Gianfranco Bazzoni, Lan Ma^§, Marie-Luise Blue^§, and Martin E. Hemler

From the  Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115 and the ^§ Bayer Research Center, West Haven, Connecticut 06516

Here we show striking differences in conformational regulation among ₁ integrins. Upon manganese stimulation, a ₁ epitope defined by monoclonal antibody (mAb) 9EG7 was induced strongly (on ₄₁), moderately (on ₅₁), weakly (on ₂₁), or was scarcely detectable (on ₆₁ and ₃₁). Comparable results were seen for the ₁ epitope defined by mAb 15/7. Likewise, soluble ligands caused strong (₄₁), moderate (₅₁), weak (₂₁, ₆₁), or minimal (₃₁) induction of the 9EG7 epitope. Exchange or deletion of  chain cytoplasmic tails did not alter Mn²⁺-induced 9EG7 epitope levels. Upon removal of calcium by EGTA or EDTA, the hierarchy of 9EG7 epitope induction was similar (₅₁ > ₂₁ > ₆₁ > ₃₁), except that EGTA reduced rather than induced 9EG7 expression on ₄₁. Thus in contrast to other ₁ integrins, calcium uniquely supports constitutive expression of the 9EG7 epitope on ₄₁. Likewise, calcium supported vascular cell adhesion molecule-stimulated 9EG7 appearance on ₄₁, whereas calcium inhibited ligand-induced 9EG7 epitope on other integrins. Constitutive expression of 9EG7 on ₄₁ was eliminated by a D698E mutation in ₄, suggesting that Asp-698 may play a key role in maintaining atypical ₄₁ response to calcium. In conclusion, our results (i) demonstrate that mAb such as 9EG7 and 15/7 have limited diagnostic utility as reporters of ligand or Mn²⁺ occupancy for ₁ integrins, (ii) indicate pronounced differences in conformational flexibilities (₄₁ > ₅₁ > ₂₁ > ₆₁ > ₃₁), (iii) allow us to hypothesize that ₁ integrins may differ markedly in conformation-dependent inside-out signaling, and (iv) have uncovered an atypical ₄₁ response to calcium that requires ₄ Asp-698.

---

Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				F. Hu and S. M. Strittmatter The N-Terminal Domain of Nogo-A Inhibits Cell Adhesion and Axonal Outgrowth by an Integrin-Specific Mechanism J. Neurosci., January 30, 2008; 28(5): 1262 - 1269. [Abstract] [Full Text] [PDF]

				J. A. DiVietro, D. C. Brown, L. A. Sklar, R. S. Larson, and M. B. Lawrence Immobilized Stromal Cell-Derived Factor-1{alpha} Triggers Rapid VLA-4 Affinity Increases to Stabilize Lymphocyte Tethers on VCAM-1 and Subsequently Initiate Firm Adhesion J. Immunol., March 15, 2007; 178(6): 3903 - 3911. [Abstract] [Full Text] [PDF]

				X. H. Yang, O. V. Kovalenko, T. V. Kolesnikova, M. M. Andzelm, E. Rubinstein, J. L. Strominger, and M. E. Hemler Contrasting Effects of EWI Proteins, Integrins, and Protein Palmitoylation on Cell Surface CD9 Organization J. Biol. Chem., May 5, 2006; 281(18): 12976 - 12985. [Abstract] [Full Text] [PDF]

				P. Monaghan, S. Gold, J. Simpson, Z. Zhang, P. H. Weinreb, S. M. Violette, S. Alexandersen, and T. Jackson The {alpha}v{beta}6 integrin receptor for Foot-and-mouth disease virus is expressed constitutively on the epithelial cells targeted in cattle J. Gen. Virol., October 1, 2005; 86(10): 2769 - 2780. [Abstract] [Full Text] [PDF]

				X. Meng, K. Cheng, O. Krohkin, A. P. Mould, M. J. Humphries, W. Ens, K. Standing, and J. A. Wilkins Evidence for the presence of a low-mass {beta}1 integrin on the cell surface J. Cell Sci., September 1, 2005; 118(17): 4009 - 4016. [Abstract] [Full Text] [PDF]

				T. Kamata, M. Handa, Y. Sato, Y. Ikeda, and S. Aiso Membrane-proximal {alpha}/{beta} Stalk Interactions Differentially Regulate Integrin Activation J. Biol. Chem., July 1, 2005; 280(26): 24775 - 24783. [Abstract] [Full Text] [PDF]

				V. Sarin, R. D Gaffin, G. A Meininger, and M. Muthuchamy Arginine-glycine-aspartic acid (RGD)-containing peptides inhibit the force production of mouse papillary muscle bundles via {alpha}5{beta}1 integrin J. Physiol., April 15, 2005; 564(2): 603 - 617. [Abstract] [Full Text] [PDF]

				G. J. Zwartz, A. Chigaev, D. C. Dwyer, T. D. Foutz, B. S. Edwards, and L. A. Sklar Real-time Analysis of Very Late Antigen-4 Affinity Modulation by Shear J. Biol. Chem., September 10, 2004; 279(37): 38277 - 38286. [Abstract] [Full Text] [PDF]

				A. Armulik, T. Velling, and S. Johansson The Integrin {beta}1 Subunit Transmembrane Domain Regulates Phosphatidylinositol 3-Kinase-dependent Tyrosine Phosphorylation of Crk-associated Substrate Mol. Biol. Cell, June 1, 2004; 15(6): 2558 - 2567. [Abstract] [Full Text] [PDF]

				E. B. Lomakina and R. E. Waugh Micromechanical Tests of Adhesion Dynamics between Neutrophils and Immobilized ICAM-1 Biophys. J., February 1, 2004; 86(2): 1223 - 1233. [Abstract] [Full Text] [PDF]

				A. Chigaev, T. Buranda, D. C. Dwyer, E. R. Prossnitz, and L. A. Sklar FRET Detection of Cellular {alpha}4-Integrin Conformational Activation Biophys. J., December 1, 2003; 85(6): 3951 - 3962. [Abstract] [Full Text] [PDF]

				X. Yan, Y. Lin, D. Yang, Y. Shen, M. Yuan, Z. Zhang, P. Li, H. Xia, L. Li, D. Luo, et al. A novel anti-CD146 monoclonal antibody, AA98, inhibits angiogenesis and tumor growth Blood, July 1, 2003; 102(1): 184 - 191. [Abstract] [Full Text] [PDF]

				M.-A. Deugnier, M. M. Faraldo, B. Janji, P. Rousselle, J. P. Thiery, and M. A. Glukhova EGF controls the in vivo developmental potential of a mammary epithelial cell line possessing progenitor properties J. Cell Biol., November 7, 2002; 159(3): 453 - 463. [Abstract] [Full Text] [PDF]

				R. F. Rotundo, T. M. Curtis, M. D. Shah, B. Gao, A. Mastrangelo, S. E. LaFlamme, and T. M. Saba TNF-alpha disruption of lung endothelial integrity: reduced integrin mediated adhesion to fibronectin Am J Physiol Lung Cell Mol Physiol, February 1, 2002; 282(2): L316 - L329. [Abstract] [Full Text] [PDF]

				X. A. Zhang, A. L. Bontrager, C. S. Stipp, S.-K. Kraeft, G. Bazzoni, L. B. Chen, and M. E. Hemler Phosphorylation of a Conserved Integrin {alpha}3 QPSXXE Motif Regulates Signaling, Motility, and Cytoskeletal Engagement Mol. Biol. Cell, February 1, 2001; 12(2): 351 - 365. [Abstract] [Full Text]

				A. L. Bodeau, A. L. Berrier, A. M. Mastrangelo, R. Martinez, and S. E. LaFlamme A functional comparison of mutations in integrin {beta} cytoplasmic domains: effects on the regulation of tyrosine phosphorylation, cell spreading, cell attachment and {beta}1 integrin conformation J. Cell Sci., January 8, 2001; 114(15): 2795 - 2807. [Abstract] [Full Text] [PDF]

				S Alais, N Allioli, C Pujades, J. Duband, O Vainio, B. Imhof, and D Dunon HEMCAM/CD146 downregulates cell surface expression of (&bgr;)1 integrins J. Cell Sci., January 5, 2001; 114(10): 1847 - 1859. [Abstract] [PDF]

				J. Werr, E. E. Eriksson, P. Hedqvist, and L. Lindbom Engagement of {beta}2 integrins induces surface expression of {beta}1 integrin receptors in human neutrophils J. Leukoc. Biol., October 1, 2000; 68(4): 553 - 560. [Abstract] [Full Text]

				J. K. Ivins, P. D. Yurchenco, and A. D. Lander Regulation of Neurite Outgrowth by Integrin Activation J. Neurosci., September 1, 2000; 20(17): 6551 - 6560. [Abstract] [Full Text] [PDF]

				B. Leitinger and N. Hogg Effects of I Domain Deletion on the Function of the beta 2 Integrin Lymphocyte Function-associated Antigen-1 Mol. Biol. Cell, February 1, 2000; 11(2): 677 - 690. [Abstract] [Full Text]

				M. J. Hewish, Y. Takada, and B. S. Coulson Integrins alpha 2beta 1 and alpha 4beta 1 Can Mediate SA11 Rotavirus Attachment and Entry into Cells J. Virol., January 1, 2000; 74(1): 228 - 236. [Abstract] [Full Text]

				J. A. Aguirre Ghiso, K. Kovalski, and L. Ossowski Tumor Dormancy Induced by Downregulation of Urokinase Receptor in Human Carcinoma Involves Integrin and MAPK Signaling J. Cell Biol., October 4, 1999; 147(1): 89 - 104. [Abstract] [Full Text] [PDF]

				L. L. Chen, A. Whitty, R. R. Lobb, S. P. Adams, and R. B. Pepinsky Multiple Activation States of Integrin alpha 4beta 1 Detected through Their Different Affinities for a Small Molecule Ligand J. Biol. Chem., May 7, 1999; 274(19): 13167 - 13175. [Abstract] [Full Text] [PDF]

				A. Mastrangelo, S. Homan, M. Humphries, and S. LaFlamme Amino acid motifs required for isolated beta cytoplasmic domains to regulate 'in trans' beta1 integrin conformation and function in cell attachment J. Cell Sci., January 1, 1999; 112(2): 217 - 229. [Abstract] [PDF]

				M. Shang, N. Koshikawa, S. Schenk, and V. Quaranta The LG3 Module of Laminin-5 Harbors a Binding Site for Integrin alpha 3beta 1 That Promotes Cell Adhesion, Spreading, and Migration J. Biol. Chem., August 24, 2001; 276(35): 33045 - 33053. [Abstract] [Full Text] [PDF]

				X. A. Zhang, A. L. Bontrager, and M. E. Hemler Transmembrane-4 Superfamily Proteins Associate with Activated Protein Kinase C (PKC) and Link PKC to Specific beta 1 Integrins J. Biol. Chem., June 29, 2001; 276(27): 25005 - 25013. [Abstract] [Full Text] [PDF]

				L. L. Chen, A. Whitty, D. Scott, W.-C. Lee, M. Cornebise, S. P. Adams, R. C. Petter, R. R. Lobb, and R. B. Pepinsky Evidence That Ligand and Metal Ion Binding to Integrin alpha 4beta 1 Are Regulated through a Coupled Equilibrium J. Biol. Chem., September 21, 2001; 276(39): 36520 - 36529. [Abstract] [Full Text] [PDF]