|
|
Blood, 1 December 2005, Vol. 106, No. 12, pp. 3907-3916.
Prepublished online as a Blood First Edition Paper on August 16, 2005; DOI 10.1182/blood-2005-03-1204.
 Previous Article | Next Article 
Submitted March 24, 2005
Accepted July 18, 2005
p130cas mediates the transforming properties of the anaplastic lymphoma kinase
Chiara Ambrogio, Claudia Voena, Andrea D Manazza, Ludovica Riera, Roberto Piva, Laura Barberis, Carlotta Costa, Guido Tarone, Paola Defilippi, Emilio Hirsch, Elisabetta Boeri Erba, Shabaz Mohammed, Ole N Jensen, Giorgio Palestro, Giorgio Inghirami, and Roberto Chiarle*
Departments of Biomedical Sciences and Human Oncology, University of Turin, Turin, Italy
Departments of Genetics, Biology, and Biochemistry, University of Turin, Turin, Italy
Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
* Corresponding author; email: roberto.chiarle{at}unito.it.
Translocations of the Anaplastic Lymphoma Kinase (ALK) gene have been described in Anaplastic Large Cells Lymphomas (ALCL) and in stromal tumors. The most frequent translocation t(2;5) generates the fusion protein NPM-ALK with intrinsic tyrosine kinase activity. Along with transformation, NPM-ALK induces morphologic changes in fibroblasts and lymphoid cells, suggesting a direct role of ALK in cell shaping. In this study, we used a mass spectrometry based proteomic approach to search for proteins involved in cytoskeleton remodelling and identified p130Cas as a novel interactor of NPM-ALK. In 293 cells, in fibroblasts as well as in human ALK positive lymphoma cell lines, NPM-ALK was able to bind p130Cas and to induce its phosphorylation. Both the effects were dependent on ALK kinase activity and on the adaptor protein Grb2 since no binding or phosphorylation were found with the kinase-dead mutant NPM-ALKK210R or in the presence of a Grb2 dominant negative protein. Phosphorylation of p130Cas by NPM-ALK was partially independent from Src kinase activity, as it was still detectable in SYF-/- cells. Finally, p130Cas-/- fibroblasts expressing NPM-ALK showed impaired actin filament depolimerization and were no longer transformed compared to wild type cells, indicating an essential role of p130Cas activation in ALK mediated transformation.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
H. M. Amin and R. Lai
Pathobiology of ALK+ anaplastic large-cell lymphoma
Blood,
October 1, 2007;
110(7):
2259 - 2267.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Galietta, R. H. Gunby, S. Redaelli, P. Stano, C. Carniti, A. Bachi, P. W. Tucker, C. J. Tartari, C.-J. Huang, E. Colombo, et al.
NPM/ALK binds and phosphorylates the RNA/DNA-binding protein PSF in anaplastic large-cell lymphoma
Blood,
October 1, 2007;
110(7):
2600 - 2609.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Voena, C. Conte, C. Ambrogio, E. Boeri Erba, F. Boccalatte, S. Mohammed, O. N. Jensen, G. Palestro, G. Inghirami, and R. Chiarle
The Tyrosine Phosphatase Shp2 Interacts with NPM-ALK and Regulates Anaplastic Lymphoma Cell Growth and Migration
Cancer Res.,
May 1, 2007;
67(9):
4278 - 4286.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Di Florio, G. Capurso, M. Milione, F. Panzuto, R. Geremia, G. D. Fave, and C. Sette
Src family kinase activity regulates adhesion, spreading and migration of pancreatic endocrine tumour cells
Endocr. Relat. Cancer,
March 1, 2007;
14(1):
111 - 124.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Piva, R. Chiarle, A. D. Manazza, R. Taulli, W. Simmons, C. Ambrogio, V. D'Escamard, E. Pellegrino, C. Ponzetto, G. Palestro, et al.
Ablation of oncogenic ALK is a viable therapeutic approach for anaplastic large-cell lymphomas
Blood,
January 15, 2006;
107(2):
689 - 697.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
