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Alternative Splicing of the Human Proto-oncogene c-H-ras Renders a New Ras Family Protein That Trafficks to Cytoplasm and Nucleus^{1 ,,2}

Centre d’Investigació Cardiovascular-Consejo Superior de Investigaciones Científicas (CIC-CSIC), Barcelona [S. G., M. B-E.], Fontlab 2000 s.l., St. Eulalia de Ronçana [J. F-L.], and Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, 08034 Barcelona [N. d. L. I., D. C., J. C. F., J. J. G.], Spain

We characterized a novel protein of the Ras family, p19 (H-RasIDX). The c-H-ras proto-oncogene undergoes alternative splicing of the exon termed IDX. We show that the alternative p19 mRNA is stable and as abundant as p21 (p21 H-Ras4A) mRNA in all of the human tissues and cell lines tested. IDX is spliced into stable mRNA in different mammalian species, which present a high degree of nucleotide conservation. Both the endogenous and the transiently expressed p19 protein are detected in COS-1 and HeLa cells and show nuclear diffuse and speckled patterns as well as cytoplasmic localization. In yeast two-hybrid assays, p19 did not interact with two known p21 effectors, Raf1 and Rin1, but was shown to interact with RACK1, a scaffolding protein that promotes multiprotein complexes in different signaling pathways. This observation suggests that p19 and p21 play differential and complementary roles in the cell.

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