| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 18, 14642-14648, May 4, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Center for Blood Research and Department of Pathology,
Harvard Medical School, Boston, Massachusetts 02115
The adhesiveness of integrins is regulated
through a process termed "inside-out" signaling. To
understand the molecular mechanism of integrin inside-out signaling, we
generated K562 stable cell lines that expressed LFA-1
(
Association of the Membrane Proximal Regions of the
and 
Subunit Cytoplasmic Domains Constrains an Integrin in the Inactive
State*
,
L
2) or Mac-1
(M2) with mutations in the cytoplasmic
domain. Complete truncation of the 2 cytoplasmic domain,
but not a truncation that retained the membrane proximal eight
residues, resulted in constitutive activation of
L2 and M2,
demonstrating the importance of this membrane proximal region in the
regulation of integrin adhesive function. Furthermore, replacement of
the L and 2 cytoplasmic domains with
acidic and basic peptides that form an -helical coiled coil caused
inactivation of L2. Association of these
artificial cytoplasmic domains was directly demonstrated. By contrast,
replacement of the L and 2 cytoplasmic
domains with two basic peptides that do not form an -helical coiled
coil activated L2. Induction of ligand
binding by the activating cytoplasmic domain mutations correlated with the induction of activation epitopes in the extracellular domain. Our data demonstrate that cytoplasmic, membrane proximal
association between integrin and subunits, constrains an
integrin in the inactive conformation.
*
This work was supported in part by National Institutes of
Health Grants CA31798 and CA31799.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of a fellowship from the Cancer Research Institute.
Present address: Millennium Pharmaceuticals, 75 Sidney St., Cambridge,
MA 02139.
§
To whom correspondence should be addressed: Tel.: 617-278-3200;
Fax: 617-278-3232.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Matsumoto, T. Kamata, J. Takagi, K. Iwasaki, and K. Yura Key Interactions in Integrin Ectodomain Responsible for Global Conformational Change Detected by Elastic Network Normal-Mode Analysis Biophys. J., September 15, 2008; 95(6): 2895 - 2908. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Parthasarathy, X. Lin, S. M. Tan, S.K. A. Law, and J. Torres Transmembrane helices that form two opposite homodimeric interactions: An asparagine scan study of {alpha}M and {beta}2 integrins Protein Sci., May 1, 2008; 17(5): 930 - 938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhu, C. V. Carman, M. Kim, M. Shimaoka, T. A. Springer, and B.-H. Luo Requirement of {alpha} and {beta} subunit transmembrane helix separation for integrin outside-in signaling Blood, October 1, 2007; 110(7): 2475 - 2483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yin, R. I. Litvinov, G. Vilaire, H. Zhu, W. Li, G. A. Caputo, D. T. Moore, J. D. Lear, J. W. Weisel, W. F. DeGrado, et al. Activation of Platelet {alpha}IIbbeta3 by an Exogenous Peptide Corresponding to the Transmembrane Domain of {alpha}IIb J. Biol. Chem., December 1, 2006; 281(48): 36732 - 36741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Pylayeva and F. G. Giancotti Development requires activation but not phosphorylation of beta1 integrins. Genes & Dev., May 1, 2006; 20(9): 1057 - 1060. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Wiedemann, J. C. Patel, J. Lim, A. Tsun, Y. van Kooyk, and E. Caron Two distinct cytoplasmic regions of the {beta}2 integrin chain regulate RhoA function during phagocytosis. J. Cell Biol., March 27, 2006; 172(7): 1069 - 1079. [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]
|
|
|
|
 |
|
 M. Semmrich, A. Smith, C. Feterowski, S. Beer, B. Engelhardt, D. H. Busch, B. Bartsch, M. Laschinger, N. Hogg, K. Pfeffer, et al. Importance of integrin LFA-1 deactivation for the generation of immune responses J. Exp. Med., June 20, 2005; 201(12): 1987 - 1998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu, C. W. Jackson, R. A. Gruppo, L. K. Jennings, and T. K. Gartner The {beta}3 subunit of the integrin {alpha}IIb{beta}3 regulates {alpha}IIb-mediated outside-in signaling Blood, June 1, 2005; 105(11): 4345 - 4352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Partridge, S. Liu, S. Kim, J. U. Bowie, and M. H. Ginsberg Transmembrane Domain Helix Packing Stabilizes Integrin {alpha}IIb{beta}3 in the Low Affinity State J. Biol. Chem., February 25, 2005; 280(8): 7294 - 7300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Mould, M. A. Travis, S. J. Barton, J. A. Hamilton, J. A. Askari, S. E. Craig, P. R. MacDonald, R. A. Kammerer, P. A. Buckley, and M. J. Humphries Evidence That Monoclonal Antibodies Directed against the Integrin {beta} Subunit Plexin/Semaphorin/Integrin Domain Stimulate Function by Inducing Receptor Extension J. Biol. Chem., February 11, 2005; 280(6): 4238 - 4246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Clark, R. Pankov, M. A. Travis, J. A. Askari, A. P. Mould, S. E. Craig, P. Newham, K. M. Yamada, and M. J. Humphries A specific {alpha}5{beta}1-integrin conformation promotes directional integrin translocation and fibronectin matrix formation J. Cell Sci., January 15, 2005; 118(2): 291 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chigaev, G. J. Zwartz, T. Buranda, B. S. Edwards, E. R. Prossnitz, and L. A. Sklar Conformational Regulation of {alpha}4{beta}1-Integrin Affinity by Reducing Agents: "INSIDE-OUT" SIGNALING IS INDEPENDENT OF AND ADDITIVE TO REDUCTION-REGULATED INTEGRIN ACTIVATION J. Biol. Chem., July 30, 2004; 279(31): 32435 - 32443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Li, R. Gorelik, V. Nanda, P. B. Law, J. D. Lear, W. F. DeGrado, and J. S. Bennett Dimerization of the Transmembrane Domain of Integrin {alpha}IIb Subunit in Cell Membranes J. Biol. Chem., June 18, 2004; 279(25): 26666 - 26673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Vinogradova, J. Vaynberg, X. Kong, T. A. Haas, E. F. Plow, and J. Qin Membrane-mediated structural transitions at the cytoplasmic face during integrin activation PNAS, March 23, 2004; 101(12): 4094 - 4099. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Schneider and D. M. Engelman Involvement of Transmembrane Domain Interactions in Signal Transduction by {alpha}/{beta} Integrins J. Biol. Chem., March 12, 2004; 279(11): 9840 - 9846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Calderwood Integrin activation J. Cell Sci., March 1, 2004; 117(5): 657 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ni, C. G. Kevil, D. C. Bullard, and D. F. Kucik Avidity Modulation Activates Adhesion under Flow and Requires Cooperativity among Adhesion Receptors Biophys. J., December 1, 2003; 85(6): 4122 - 4133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kim, C. V. Carman, and T. A. Springer Bidirectional Transmembrane Signaling by Cytoplasmic Domain Separation in Integrins Science, September 19, 2003; 301(5640): 1720 - 1725. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-M. Xiong, J. Chen, and L. Zhang Modulation of CD11b/CD18 Adhesive Activity by Its Extracellular, Membrane-Proximal Regions J. Immunol., July 15, 2003; 171(2): 1042 - 1050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-H. Luo, T. A. Springer, and J. Takagi High Affinity Ligand Binding by Integrins Does Not Involve Head Separation J. Biol. Chem., May 2, 2003; 278(19): 17185 - 17189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. F. DeGrado, H. Gratkowski, and J. D. Lear How do helix-helix interactions help determine the folds of membrane proteins? Perspectives from the study of homo-oligomeric helical bundles Protein Sci., April 1, 2003; 12(4): 647 - 665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, Z. Li, E.-K. Viklund, and S. Stromblad p21-activated kinase 4 interacts with integrin {alpha}v{beta}5 and regulates {alpha}v{beta}5-mediated cell migration J. Cell Biol., September 29, 2002; 158(7): 1287 - 1297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.C. Liddington and M.H. Ginsberg Integrin activation takes shape J. Cell Biol., September 3, 2002; 158(5): 833 - 839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Gottschalk, P. D. Adams, A. T. Brunger, and H. Kessler Transmembrane signal transduction of the {alpha}IIb{beta}3 integrin Protein Sci., July 1, 2002; 11(7): 1800 - 1812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Mould, J. A. Askari, S. Barton, A. D. Kline, P. A. McEwan, S. E. Craig, and M. J. Humphries Integrin Activation Involves a Conformational Change in the alpha 1 Helix of the beta Subunit A-domain J. Biol. Chem., May 24, 2002; 277(22): 19800 - 19805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Weljie, P. M. Hwang, and H. J. Vogel Solution structures of the cytoplasmic tail complex from platelet integrin alpha IIb- and beta 3-subunits PNAS, April 30, 2002; 99(9): 5878 - 5883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Li, C. R. Babu, J. D. Lear, A. J. Wand, J. S. Bennett, and W. F. DeGrado Oligomerization of the integrin alpha IIbbeta 3: Roles of the transmembrane and cytoplasmic domains PNAS, October 12, 2001; (2001) 221463098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Takagi, N. Beglova, P. Yalamanchili, S. C. Blacklow, and T. A. Springer Definition of EGF-like, closely interacting modules that bear activation epitopes in integrin beta subunits PNAS, September 25, 2001; 98(20): 11175 - 11180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Ginsberg, B. Yaspan, J. Forsyth, T. S. Ulmer, I. D. Campbell, and M. Slepak A Membrane-distal Segment of the Integrin alpha IIb Cytoplasmic Domain Regulates Integrin Activation J. Biol. Chem., June 15, 2001; 276(25): 22514 - 22521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Li, C. R. Babu, J. D. Lear, A. J. Wand, J. S. Bennett, and W. F. DeGrado Oligomerization of the integrin alpha IIbbeta 3: Roles of the transmembrane and cytoplasmic domains PNAS, October 23, 2001; 98(22): 12462 - 12467. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
