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 Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Petruzzelli, L. Articles by Springer, T. A. Search for Related Content PubMed PubMed Citation Articles by Petruzzelli, L. Articles by Springer, T. A. Pubmed/NCBI databases Substance via MeSH

Differential Requirements for LFA-1 Binding to ICAM-1 and LFA-1-Mediated Cell Aggregation¹

Harvard Medical School, Center for Blood Research, Boston, MA 02115

Cellular adhesion through the ß₂ integrin lymphocyte function-associated Ag (LFA)-1 is a complex event involving activation, ligand binding, and cell shape changes that ultimately result in enhanced adhesion. In this report we define requirements for ligand binding and post receptor signaling by comparing two mechanisms of activation of LFA-1: 1) inside-out signaling and 2) direct activation by the ß₂ Ab, CBR LFA-1/2. Our results demonstrate that activation of LFA-1 binding to ICAM-1 by CBR LFA-1/2, in contrast to inside-out signaling mechanisms, does not require protein kinase C activation or protein phosphatase 2A activity nor is it affected by agents that interfere with reorganization of the cytoskeleton. Inhibition of protein tyrosine kinase activity does not affect ICAM-1 binding by either mechanism of activation. However, activation by either mode does require the presence of the ß cytoplasmic domain; deletion of the C-terminal phenylalanine or the five amino acid stretch between 756–762 abolished activation of LFA-1. This, combined with the observation that intracellular energy pools must be preserved, implicates the ß cytoplasmic domain in a key energy-dependent conformational change in LFA-1 that is required to achieve enhanced ligand binding. Post ligand binding events induced by both PMA and Ab stimulation, as measured by homotypic aggregation, require protein tyrosine kinase, phosphatase, and RhoA activities. By examining both ligand binding and aggregation, we have been able to dissect the signaling components critical in the multistep process of LFA-1-mediated cellular adhesion.

This article has been cited by other articles:

				Z. Jevnikar, N. Obermajer, M. Bogyo, and J. Kos The role of cathepsin X in the migration and invasiveness of T lymphocytes J. Cell Sci., August 15, 2008; 121(16): 2652 - 2661. [Abstract] [Full Text] [PDF]

				J. Lomas-Neira, C.-S. Chung, M. Perl, S. Gregory, W. Biffl, and A. Ayala Role of alveolar macrophage and migrating neutrophils in hemorrhage-induced priming for ALI subsequent to septic challenge Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L51 - L58. [Abstract] [Full Text] [PDF]

				L. Liu, B. R. Schwartz, J. Tupper, N. Lin, R. K. Winn, and J. M. Harlan The GTPase Rap1 Regulates Phorbol 12-Myristate 13-Acetate-stimulated but Not Ligand-induced beta 1 Integrin-dependent Leukocyte Adhesion J. Biol. Chem., October 18, 2002; 277(43): 40893 - 40900. [Abstract] [Full Text] [PDF]

				L. Liu, B. R. Schwartz, N. Lin, R. K. Winn, and J. M. Harlan Requirement for RhoA Kinase Activation in Leukocyte De-Adhesion J. Immunol., September 1, 2002; 169(5): 2330 - 2336. [Abstract] [Full Text] [PDF]

				S. J. Hyduk and M. I. Cybulsky {alpha}4 Integrin Signaling Activates Phosphatidylinositol 3-Kinase and Stimulates T Cell Adhesion to Intercellular Adhesion Molecule-1 to a Similar Extent As CD3, but Induces a Distinct Rearrangement of the Actin Cytoskeleton J. Immunol., January 15, 2002; 168(2): 696 - 704. [Abstract] [Full Text] [PDF]

				R. A. Worthylake, S. Lemoine, J. M. Watson, and K. Burridge RhoA is required for monocyte tail retraction during transendothelial migration J. Cell Biol., July 9, 2001; 154(1): 147 - 160. [Abstract] [Full Text] [PDF]

				N. J. Borthwick, M. Lowdell, M. Salmon, and A. N. Akbar Loss of CD28 expression on CD8+ T cells is induced by IL-2 receptor {gamma} chain signalling cytokines and type I IFN, and increases susceptibility to activation-induced apoptosis Int. Immunol., July 1, 2000; 12(7): 1005 - 1013. [Abstract] [Full Text] [PDF]

				I. S. Douglas, A. R. Leff, and A. I. Sperling CD4+ T Cell and Eosinophil Adhesion Is Mediated by Specific ICAM-3 Ligation and Results in Eosinophil Activation J. Immunol., March 15, 2000; 164(6): 3385 - 3391. [Abstract] [Full Text] [PDF]

				L. Liu, P. Moesner, N. L. Kovach, R. Bailey, A. D. Hamilton, S. M. Sebti, and J. M. Harlan Integrin-dependent Leukocyte Adhesion Involves Geranylgeranylated Protein(s) J. Biol. Chem., November 19, 1999; 274(47): 33334 - 33340. [Abstract] [Full Text] [PDF]

				A. Kotovuori, T. Pessa-Morikawa, P. Kotovuori, P. Nortamo, and C. G. Gahmberg ICAM-2 and a Peptide from Its Binding Domain Are Efficient Activators of Leukocyte Adhesion and Integrin Affinity J. Immunol., June 1, 1999; 162(11): 6613 - 6620. [Abstract] [Full Text] [PDF]

				D. W. Griggs, C. M. Schmidt, and C. P. Carron Characteristics of Cation Binding to the I Domains of LFA-1 and MAC-1. THE LFA-1 I DOMAIN CONTAINS A Ca2+-BINDING SITE J. Biol. Chem., August 21, 1998; 273(34): 22113 - 22119. [Abstract] [Full Text] [PDF]

				E. S. Harris, T. M. McIntyre, S. M. Prescott, and G. A. Zimmerman The Leukocyte Integrins J. Biol. Chem., July 28, 2000; 275(31): 23409 - 23412. [Full Text] [PDF]