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Intracellular translocation of the decapeptide carboxyl terminal of G(i)3 alpha induces the dual phosphorylation of p42/p44 MAP kinases
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UNSPECIFIED. (2005) Intracellular translocation of the decapeptide carboxyl terminal of G(i)3 alpha induces the dual phosphorylation of p42/p44 MAP kinases. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1745 (2). pp. 207-214. ISSN 0167-4889
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Official URL: http://dx.doi.org/10.1016/j.bbamcr.2005.05.006
Abstract
The carboxyl terminal of heterotrimeric G protein alpha subunits binds both G protein-coupled receptors and mastoparan (MP), a tetradecapeptide allostere. Moreover, peptides corresponding to the carboxyl domains of G(i)3 alpha and G(t) display intrinsic biological activities in cell-free systems. Thus, the purpose of this study was to develop a cell penetrant delivery system to further investigate the biological properties of a peptide mimetic of the G(i)3 alpha carboxyl terminal (G(i)3 alpha(346-355); H-KNNLKECGLY-NH2). Kinetic studies, using a CFDA-conjugated analogue of G(i)3 alpha(346-355), confirmed the rapid and efficient intracellular translocation of TP10-G(i)3 alpha(346-355) (t(0.5) = 3 min). Translocated G(i)3 alpha(346-355), but not other bioactive cargoes derived from PKC and the CB1 cannabinoid receptor, promoted the dual phosphorylation of p42/p44 MAPK without adverse changes in cellular viability. The relative specificity of this novel biological activity was further confirmed by the observation that translocated G(i)3 alpha(346-355) did not influence the exocytosis of beta-hexoseaminidase from RBL-2H3, a secretory event stimulated by other cell penetrant peptide cargoes and MP. We conclude that TP10-G(i)3 alpha(346-355) is a valuable, non-toxic research tool with which to study and modulate signal transduction pathways mediated by heterotrimeric G proteins and MAPK. (c) 2005 Elsevier B.V. All rights reserved.
| Item Type: | Journal Article |
|---|---|
| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology |
| Journal or Publication Title: | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH |
| Publisher: | ELSEVIER SCIENCE BV |
| ISSN: | 0167-4889 |
| Date: | 10 September 2005 |
| Volume: | 1745 |
| Number: | 2 |
| Number of Pages: | 8 |
| Page Range: | pp. 207-214 |
| Identification Number: | 10.1016/j.bbamcr.2005.05.006 |
| Publication Status: | Published |
| URI: | http://wrap.warwick.ac.uk/id/eprint/6634 |
Data sourced from Thomson Reuters' Web of Knowledge
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