Intracellular translocation of the decapeptide carboxyl terminal of Gi3 alpha induces the dual phosphorylation of p42/p44 MAP kinases.

2.50
Hdl Handle:
http://hdl.handle.net/2436/15802
Title:
Intracellular translocation of the decapeptide carboxyl terminal of Gi3 alpha induces the dual phosphorylation of p42/p44 MAP kinases.
Authors:
Jones, Sarah; Farquhar, Michelle; Martin, Ashley; Howl, John D.
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)3alpha 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)3alpha carboxyl terminal (G(i)3alpha(346-355); H-KNNLKECGLY-NH2). Kinetic studies, using a CFDA-conjugated analogue of G(i)3alpha(346-355), confirmed the rapid and efficient intracellular translocation of TP10-G(i)3alpha(346-355) (t(0.5) = 3 min). Translocated G(i)3alpha(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)3alpha(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)3alpha(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.
Citation:
Biochimica Biophysica Acta - Molecular Cell Research, 1745(2): 207-214
Publisher:
Elsevier BV
Issue Date:
2005
URI:
http://hdl.handle.net/2436/15802
DOI:
10.1016/j.bbamcr.2005.05.006
PubMed ID:
15953648
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T20-4G98WPV-2&_user=1644469&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000054077&_version=1&_urlVersion=0&_userid=1644469&md5=562f7956021f4bd397af6452096f9d8a
Type:
Article
Language:
en
Description:
Metadata only
ISSN:
0006-3002
Appears in Collections:
Molecular Pharmacology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorJones, Sarah-
dc.contributor.authorFarquhar, Michelle-
dc.contributor.authorMartin, Ashley-
dc.contributor.authorHowl, John D.-
dc.date.accessioned2008-01-08T10:49:31Z-
dc.date.available2008-01-08T10:49:31Z-
dc.date.issued2005-
dc.identifier.citationBiochimica Biophysica Acta - Molecular Cell Research, 1745(2): 207-214en
dc.identifier.issn0006-3002-
dc.identifier.pmid15953648-
dc.identifier.doi10.1016/j.bbamcr.2005.05.006-
dc.identifier.urihttp://hdl.handle.net/2436/15802-
dc.descriptionMetadata onlyen
dc.description.abstractThe 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)3alpha 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)3alpha carboxyl terminal (G(i)3alpha(346-355); H-KNNLKECGLY-NH2). Kinetic studies, using a CFDA-conjugated analogue of G(i)3alpha(346-355), confirmed the rapid and efficient intracellular translocation of TP10-G(i)3alpha(346-355) (t(0.5) = 3 min). Translocated G(i)3alpha(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)3alpha(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)3alpha(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.en
dc.language.isoenen
dc.publisherElsevier BVen
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T20-4G98WPV-2&_user=1644469&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000054077&_version=1&_urlVersion=0&_userid=1644469&md5=562f7956021f4bd397af6452096f9d8aen
dc.subjectMastoparanen
dc.subjectSecretionen
dc.subjectp42/p44 MAP kinaseen
dc.subjectG proteinen
dc.subjectCell Penetrating Peptides (CPP)en
dc.subjectSignallingen
dc.titleIntracellular translocation of the decapeptide carboxyl terminal of Gi3 alpha induces the dual phosphorylation of p42/p44 MAP kinases.en
dc.typeArticleen
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