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Mysliwiec T , Perego R , Kruh GD
Analysis of chimeric Gag-Arg/Abl molecules indicates a distinct negative regulatory role for the Arg C-terminal domain
Oncogene. 1996 Feb 1;12(3) :631-640
PMID: ISI:A1996TV59700020   
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Abstract
Arg and c-Abl represent the mammalian member of the Abelson family of nonreceptor protein tyrosine kinases. The two proteins are composed of SH2, SH3, kinase and C-terminal domains, To examine Arg structure-function relationships we analysed a Gag-Arg fusion protein, analogous to the oncogenic Gag-Abl fusion protein of Abelson Murine Leukaemia Virus and found that in contrast to Gag-Abl, it lacked transforming activity, Three observations indicated that the difference in the transforming activity was mediated by the distinct Arg and Abl C-terminal domains, (1) The analysis of chimeric Gag- Arg/Abl molecules revealed that the Arg C-terminal domain completely abrogated Gag-Abl transforming activity and that the Abl C-terminus conferred transforming activity to Gag-Arg, Substitutions of SH2 and kinase domains did not affect activity, (2) Alterations in the Arg C-terminus were observed in spontaneous foci that developed in transfections of two nontransforming chimera. (3) An engineered Gag-Arg molecule containing a truncation of almost the entire C-terminal domain, including three SH3 domain-binding sites, was oncogenic, whereas a slightly smaller truncation that deleted two of three SH3 domain-binding sites, lacked transforming activity, These observations indicate that the C-terminal domain regulates Arg biological activity in a manner distinct from c-Abl and suggest that this effect may be mediated in part by SH3 domain-binding sites.
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Times Cited: 13 English Article TV597 ONCOGENE