Homo- and hetero-oligomerization of the c-Abl kinase and Abelson-interactor-1.

Pang-Dian Fan, Feng Cong, Stephen P Goff

Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

Cancer research 2003 Feb 15

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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.

Citation

Pang-Dian Fan, Feng Cong, Stephen P Goff. Homo- and hetero-oligomerization of the c-Abl kinase and Abelson-interactor-1. Cancer research. 2003 Feb 15;63(4):873-7