|
|
Prepublished online as a Blood First Edition Paper on June 5, 2003; DOI 10.1182/blood-2003-01-0062.
 Previous Article | Table of Contents | Next Article 
Blood, 15 September 2003, Vol. 102, No. 6, pp. 2220-2228
NEOPLASIA
Localization of BCR-ABL to F-actin regulates cell adhesion but does not attenuate CML development
Jason A. Wertheim,
Samanthi A. Perera,
Daniel A. Hammer,
Ruibao Ren,
David Boettiger, and
Warren S. Pear
From the Department of Pathology and Laboratory Medicine, Institute for Medicine and Engineering, Abramson Family Cancer Research Institute, Department of Bioengineering, and Department of Microbiology, University of Pennsylvania, Philadelphia; and Rosenstiel Basic Medical Sciences Research Center, Department of Biology, Brandeis University, Waltham, MA.
We have previously found that P210BCR-ABL increases the adhesion of hematopoietic cell lines to fibronectin by a mechanism that is independent of tyrosine kinase activity. To investigate the pathway(s) by which P210BCR-ABL influences cell adhesion, we used a quantitative cell adhesion device that can discern small changes in cell adhesion to assay P210BCR-ABL with mutations in several critical domains. We expressed P210BCR-ABL mutants in 32D myeloblast cells and found that binding to fibronectin is mediated primarily by the  5 1 integrin. We performed a structure/function analysis to map domains important for cell adhesion. Increased adhesion was mediated by 3 domains: (1) the N-terminal coiled-coil domain that facilitates oligomerization and F-actin localization; (2) bcr sequences between aa 163 to 210; and (3) F-actin localization through the C-terminal actin-binding domain of c-abl. We compared our adhesion results with the ability of these mutants to cause a chronic myelogenous leukemia (CML)–like disease in a murine bone marrow transplantation assay and found that adhesion to fibronectin did not correlate with the ability of these mutants to cause CML. Together, our results suggest that F-actin localization may play a pivotal role in modulating adhesion but that it is dispensable for the development of CML.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Chu, L. Li, H. Singh, and R. Bhatia
BCR-Tyrosine 177 Plays an Essential Role in Ras and Akt Activation and in Human Hematopoietic Progenitor Transformation in Chronic Myelogenous Leukemia
Cancer Res.,
July 15, 2007;
67(14):
7045 - 7053.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Li, N. Clough, X. Sun, W. Yu, B. L. Abbott, C. J. Hogan, and Z. Dai
Bcr-Abl induces abnormal cytoskeleton remodeling, beta1 integrin clustering and increased cell adhesion to fibronectin through the Abl interactor 1 pathway
J. Cell Sci.,
April 15, 2007;
120(8):
1436 - 1446.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. McCallum, S. Price, N. Planque, B. Perbal, A. Pierce, A. D. Whetton, and A. E. Irvine
A novel mechanism for BCR-ABL action: stimulated secretion of CCN3 is involved in growth and differentiation regulation
Blood,
September 1, 2006;
108(5):
1716 - 1723.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Ramaraj, H. Singh, N. Niu, S. Chu, M. Holtz, J. K. Yee, and R. Bhatia
Effect of Mutational Inactivation of Tyrosine Kinase Activity on BCR/ABL-Induced Abnormalities in Cell Growth and Adhesion in Human Hematopoietic Progenitors
Cancer Res.,
August 1, 2004;
64(15):
5322 - 5331.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
