|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online 4 January 2005
doi: 10.1242/jcs.01625
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research Article |
1 Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
2 Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2-1 Hiroshwa, Wako-shi Saitama 351-01, Japan
3 Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
* Author for correspondence (e-mail: foxj{at}ccf.org)
Accepted 2 November 2004
In this study, we used cultured cells spreading on ß3 integrin substrates to examine the possibility that spectrin is involved in signal transduction. Spectrin clustered with specialized calpain-induced ß3 integrin signaling complexes that mediate the initial attachment of cells and initiate Rac activation and lamellipodia extension. It was absent from focal complexes and focal adhesions, the integrin complexes that mediate adhesion in lamellipodia and fully spread cells. Spectrin contains a Src homology (SH3) domain of unknown function. Cells overexpressing this domain adhered and calpain-induced integrin signaling complexes formed. However, Rac activation, lamellipodia extension and cell spreading were inhibited. Spreading was restored by overexpression of constitutively active Rac. These studies point to a previously unrecognized role for spectrin and its SH3 domain in initiating Rac activation in the specialized integrin clusters that initiate cell adhesion and spreading. Thus, spectrin may have a pivotal role in initiating integrin-induced physiological and pathological events such as development, proliferation, cell survival, wound healing, metastasis and atherosclerosis.
Key words: Spectrin, SH3 domain, Cell spreading, ß3 integrin, Calpain, Rac activation
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Metral, B. Machnicka, S. Bigot, Y. Colin, D. Dhermy, and M.-C. Lecomte {alpha}II-Spectrin Is Critical for Cell Adhesion and Cell Cycle J. Biol. Chem., January 23, 2009; 284(4): 2409 - 2418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hulsmeier, J. Pielage, C. Rickert, G. M. Technau, C. Klambt, and T. Stork Distinct functions of {alpha}-Spectrin and {beta}-Spectrin during axonal pathfinding Development, February 15, 2007; 134(4): 713 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Helfer, B. C. Boswell, D. Finlay, A. Cipres, K. Vuori, T. Bong Kang, D. Wallach, A. Dorfleutner, J. M. Lahti, D. C. Flynn, et al. Caspase-8 Promotes Cell Motility and Calpain Activity under Nonapoptotic Conditions. Cancer Res., April 15, 2006; 66(8): 4273 - 4278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Street, S. J. Marsh, P. R. Stabach, J. S. Morrow, D. A. Brown, and N. J. Buckley Stimulation of G{alpha}q-coupled M1 muscarinic receptor causes reversible spectrin redistribution mediated by PLC, PKC and ROCK J. Cell Sci., April 15, 2006; 119(8): 1528 - 1536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Franco and A. Huttenlocher Regulating cell migration: calpains make the cut J. Cell Sci., September 1, 2005; 118(17): 3829 - 3838. [Abstract] [Full Text] [PDF]
|
|
