Back to Search
Start Over
Bcr/Abl P190 interaction with Spa-1, a GTPase activating protein for the small GTPase Rap1.
- Source :
-
International journal of molecular medicine [Int J Mol Med] 2008 Oct; Vol. 22 (4), pp. 453-8. - Publication Year :
- 2008
-
Abstract
- The Bcr/Abl oncogene is responsible for the development of Ph-chromosome positive acute lymphoblastic leukemia and chronic myelogenous leukemia in humans. Previous studies demonstrated that Bcr/Abl expression is associated with elevated levels of activated Rap1, a small GTPase. Levels of activated Rap1 are determined by a balance between GTPase activating and G-nucleotide exchange factor activity. We show that Bcr/Abl forms a protein-protein complex with Spa-1, a GTPase activating protein for Rap1, both in COS-1 cells as well as in primary lymphoblastic leukemia cells from a transgenic P190 BCR/ABL mouse model. The interaction between Spa-1 and P190 did not affect the tyrosine kinase activity of P190, nor did Spa-1 become phosphorylated on tyrosine as a result of the interaction. P190 and Spa-1 co-localized to peripheral actin structures in primary lymphoblasts and expression of Spa-1 in the leukemic lymphoblasts decreased the migration of these cells. The binding of Bcr/Abl to Spa-1 may cause aberrant subcellular location of Spa-1 and affect migration of these cells.
- Subjects :
- Animals
COS Cells
Cattle
Cell Line, Tumor
Cell Lineage
Chlorocebus aethiops
Humans
Immunoprecipitation
Mice
Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism
Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology
Protein Binding
Protein Transport
Proto-Oncogene Proteins c-abl metabolism
Fusion Proteins, bcr-abl metabolism
GTPase-Activating Proteins metabolism
Monomeric GTP-Binding Proteins metabolism
Nuclear Proteins metabolism
rap1 GTP-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1107-3756
- Volume :
- 22
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 18813851