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, Warren S. Pear*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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 P21OBCR-ABL influences cell adhesion, we used a quantitative cell adhesion device that can discern small changes in cell adhesion to assay P21OBCR-ABL with mutations in several critical domains. We expressed P21OBCR-ABL mutants in 32D myeloblast cells and found that binding to fibronectin is mediated primarily by the α5β 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.

Original languageEnglish (US)
Pages (from-to)2220-2228
Number of pages9
JournalBlood
Volume102
Issue number6
DOIs
StatePublished - Sep 15 2003

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Localization of BCR-ABL to F-actin regulates cell adhesion but does not attenuate CML development'. Together they form a unique fingerprint.

Cite this