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.
journal_name
Oncogenejournal_title
Oncogeneauthors
Mysliwiec T,Perego R,Kruh GDsubject
Has Abstractpub_date
1996-02-01 00:00:00pages
631-40issue
3eissn
0950-9232issn
1476-5594journal_volume
12pub_type
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