Bcr/Abl P190 interaction with Spa-1, a GTPase activating protein for the small GTPase Rap1.
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.
Yi
Sun-Ju
SJ
Section of Molecular Carcinogenesis, The Saban Research Institute of Childrens Hospital, Los Angeles, Los Angeles, CA 90027, USA.
Lee
Hyung-Taek
HT
Groffen
John
J
Heisterkamp
Nora
N
D000818:Animals; D019556:COS Cells; D002417:Cattle; D045744:Cell Line, Tumor; D019070:Cell Lineage; D002522:Chlorocebus aethiops; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D021381:Protein Transport; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C091108:Sipa1 protein, mouse; D016044:Fusion Proteins, bcr-abl; D016315:Proto-Oncogene Proteins c-abl; D020559:Monomeric GTP-Binding Proteins; D020827:rap1 GTP-Binding Proteins