Homo- and hetero-oligomerization of the c-Abl kinase and Abelson-interactor-1.
Oligomerization of the nonreceptor tyrosine kinase c-Abl can activate its transforming potential. Domains mediating oligomerization within the BCR-ABL and TEL-ABL oncoproteins are required for transforming activity, and fusion of inducible dimerization domains to c-Abl can generate chimeric proteins with dimerization-dependent transforming activity. We have found that c-Abl oligomerizes at high levels of expression in COS cells. This interaction is dependent on kinase activity and an intact NH(2)-terminal region of c-Abl. A binding partner of c-Abl, Abl-interactor-1 (Abi-1), similarly oligomerizes in COS cells. An oligomeric form of Abi-1 interacts with Abl both in vitro and in mammalian cells. These results suggest the possibility that oligomerization of Abl kinases, perhaps involving regulation by their interaction partners, may play a role in modulation of kinase activity in both normal and oncogenic processes.
Fan
Pang-Dian
PD
Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Cong
Feng
F
Goff
Stephen P
SP
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins; D000939:Epitopes / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011485:Protein Binding; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism; D014162:Transfection
C513733:ABI1 protein, human; C513734:Abi1 protein, mouse; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D000939:Epitopes; D018398:Homeodomain Proteins; D016315:Proto-Oncogene Proteins c-abl