Linked Life Data

12010816

Source:http://linkedlifedata.com/resource/pubmed/id/12010816

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2002-5-15
pubmed:abstractText
The t(9;22) chromosomal translocation results in expression of P210(BCR-ABL), a fusion protein necessary for the development of chronic myelogenous leukemia (CML). The constitutive activation of the P210(BCR-ABL) tyrosine kinase results in phosphorylation of multiple signaling pathways leading to the transformed phenotype. Additionally, extracellular interactions between P210(BCR-ABL)-expressing progenitor cells and bone marrow stroma may provide external signals that facilitate CML development. In contrast to the intracellular signaling pathways involved in CML, little is known about how P210(BCR-ABL) expression modifies cell-cell and cell-substratum interactions. To investigate the role of P210(BCR-ABL) in modulating cellular adhesion, we used a highly sensitive and quantitative cell detachment apparatus that measures the strength of association between a population of cells and an adhesive matrix. Our findings show that P210(BCR-ABL) expression increased adhesion nearly 2-fold between the myeloblastic cell line, 32D, and fibronectin compared to a control vector. We then investigated whether abnormal adhesion due to P210(BCR-ABL) expression was caused by its tyrosine kinase activity. A quantitative analysis of cell-fibronectin adhesion found that neither expression of a kinase-inactive P210(BCR-ABL) mutant in 32D cells or attenuation of kinase activity by STI571 (imatinib mesylate) in 32D cells transduced with wild-type P210(BCR-ABL) could correct the nearly 2-fold increase in cell-fibronectin adhesion. Similarly, STI571 treatment of Meg-01 cells, a P210(BCR-ABL)-expressing cell line derived from a patient in blast crisis, failed to inhibit adhesion to fibronectin. Together, our results indicate that changes in adhesion induced by P210(BCR-ABL) are independent of its tyrosine kinase activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4122-30
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12010816-3T3 Cells, pubmed-meshheading:12010816-Amino Acid Substitution, pubmed-meshheading:12010816-Animals, pubmed-meshheading:12010816-Cell Adhesion, pubmed-meshheading:12010816-Cell Line, pubmed-meshheading:12010816-Chromosomes, Human, Pair 22, pubmed-meshheading:12010816-Chromosomes, Human, Pair 9, pubmed-meshheading:12010816-Flow Cytometry, pubmed-meshheading:12010816-Fusion Proteins, bcr-abl, pubmed-meshheading:12010816-Humans, pubmed-meshheading:12010816-Megakaryocytes, pubmed-meshheading:12010816-Mice, pubmed-meshheading:12010816-Piperazines, pubmed-meshheading:12010816-Protein-Tyrosine Kinases, pubmed-meshheading:12010816-Pyrimidines, pubmed-meshheading:12010816-Recombinant Proteins, pubmed-meshheading:12010816-Transfection, pubmed-meshheading:12010816-Translocation, Genetic
pubmed:year
2002
pubmed:articleTitle
BCR-ABL-induced adhesion defects are tyrosine kinase-independent.
pubmed:affiliation
Department of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia 19104-6160, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't