| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Scientific Institute San Raffaele-DIBIT, and
University of Milan School of Medicine, Milan, Italy;
Department of Biochemistry, Free University of Berlin, Berlin, Germany; and
§
Molecular Cardiobiology, Boyer Center for Molecular Medicine, Cardiovascular Medicine, and the Raymond and Beverly Sackler Cardiobiology Laboratory, Yale University School of Medicine, New Haven, CT 06536
Anchorage dependence defines the cellular requirement for integrin-mediated adhesion to substrate to initiate DNA replication in response to growth factors. In this study we investigated whether normal T cells, which spend extended periods in a nonadherent state, show similar requirements for cell cycle progression in response to TCR stimulation. Resting primary T lymphocytes were induced to enter the cell cycle by TCR triggering, and leukocyte integrins were either engaged using purified ICAM-1 or inhibited with function-blocking mAbs. Our data indicate that leukocyte integrins complement TCR-driven mitogenic signals not as a result of their direct clustering but, rather, via integrin-dependent organization of the actin cytoskeleton. Leukocyte integrin-dependent reorganization of the actin cytoskeleton cooperates with the TCR to effect mitogen-activated protein kinase activation, but also represents a required late (4–8 h poststimulation) component in the mitogenic response of normal T cells. Prolonged leukocyte integrin-dependent spreading, in the context of intercellular contact, is a requisite for the production of the mitogenic cytokine IL-2, which, in turn, is involved in the induction of D3 cyclin and is primarily responsible for the decrease in the cyclin-dependent kinase inhibitor p27kip, resulting in retinoblastoma protein inactivation and S phase entry. Thus, T lymphocytes represent a peculiar case of anchorage dependence, in which signals conveyed by integrins act sequentially with the activating stimulus to effect a sustained production of the essential mitogenic cytokine.
This article has been cited by other articles:
|
|
 |
|
  S. M. Nurmi, M. Autero, A. K. Raunio, C. G. Gahmberg, and S. C. Fagerholm Phosphorylation of the LFA-1 Integrin beta2-Chain on Thr-758 Leads to Adhesion, Rac-1/Cdc42 Activation, and Stimulation of CD69 Expression in Human T Cells J. Biol. Chem., January 12, 2007; 282(2): 968 - 975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-i. Suzuki, S. Yamasaki, J. Wu, G. A. Koretzky, and T. Saito The actin cloud induced by LFA-1-mediated outside-in signals lowers the threshold for T-cell activation Blood, January 1, 2007; 109(1): 168 - 175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Wang, M. Collinge, V. Ramgolam, O. Ayalon, X. C. Fan, R. Pardi, and J. R. Bender LFA-1-Dependent HuR Nuclear Export and Cytokine mRNA Stabilization in T Cell Activation J. Immunol., February 15, 2006; 176(4): 2105 - 2113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sturm, K. A. Krivacic, C. Fiocchi, and A. D. Levine Dual Function of the Extracellular Matrix: Stimulatory for Cell Cycle Progression of Naive T Cells and Antiapoptotic for Tissue-Derived Memory T Cells J. Immunol., September 15, 2004; 173(6): 3889 - 3900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Denti, A. Sirri, A. Cheli, L. Rogge, G. Innamorati, S. Putignano, M. Fabbri, R. Pardi, and E. Bianchi RanBPM Is a Phosphoprotein That Associates with the Plasma Membrane and Interacts with the Integrin LFA-1 J. Biol. Chem., March 26, 2004; 279(13): 13027 - 13034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Abraham and J. Miller Molecular Mechanisms of IL-2 Gene Regulation Following Costimulation Through LFA-1 J. Immunol., November 1, 2001; 167(9): 5193 - 5201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Somasundaram, M. Ruehl, N. Tiling, R. Ackermann, M. Schmid, E. O. Riecken, and D. Schuppan Collagens Serve as an Extracellular Store of Bioactive Interleukin 2 J. Biol. Chem., December 1, 2000; 275(49): 38170 - 38175. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
