Subcellular localization of the Arg protein tyrosine kinase.

Arg and c-Abl are ubiquitously expressed proteins which represent the mammalian members of the Abelson family of nonreceptor protein tyrosine kinases (PTKs). In contrast to most nonreceptor PTKs, c-Abl is located in the nucleus and cytoplasm. In this study the subcellular localization of Arg was examined to gain insight into its possible functions. Using indirect immunofluorescence, Arg was detected in the cytoplasm but not the nucleus of both transiently transfected COS cells and stable NIH3T3 transfectants. Arg is expressed as IA and IB isoforms which bear alternative amino termini, with the IB isoform containing a potential myristic acid acceptor sequence. Modification of ArgIB by myristic acid was confirmed by the detection of [3H]myristic acid labeling and the observation that labeling was abolished by mutating Gly-2. These results indicate that the subcellular localization of Arg is distinct from that of c-Abl and thus suggest that the two proteins have different functions in intracellular signaling. In addition, Arg, like c-Abl, is expressed as myristoylated and nonmyristoylated isoforms, suggesting that it may have dual cytoplasmic subcellular localizations, and possibly participate in diverse signaling pathways.