Intracellular peptides as natural regulators of cell signaling

Intracellular peptides as natural regulators of cell signaling

Autor Cunha, Fernanda Marques da Autor UNIFESP Google Scholar
Berti, Denise A. Google Scholar
Ferreira, Zulma S. Google Scholar
Klitzke, Clecio F. Google Scholar
Markus, Regina P. Google Scholar
Ferro, Emer Suavinho Autor UNIFESP Google Scholar
Instituição Butantan Inst
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Resumo Protein degradation by the ubiquitin proteasome system releases large amounts of oligopeptides within cells. To investigate possible functions for these intracellularly generated oligopeptides, we fused them to a cationic transactivator peptide sequence using reversible disulfide bonds, introduced them into cells, and analyzed their effect on G protein-coupled receptor (GPCR) signal transduction. A mixture containing four of these peptides (20-80 mu M) significantly inhibited the increase in the extracellular acidification response triggered by angiotensin II (ang II) in CHO-S cells transfected with the ang II type 1 receptor (AT1R-CHO-S). Subsequently, either alone or in a mixture, these peptides increased luciferase gene transcription in AT1R-CHO-S cells stimulated with ang II and in HEK293 cells treated with isoproterenol. These peptides without transactivator failed to affect GPCR cellular responses. All four functional peptides were shown in vitro to competitively inhibit the degradation of a synthetic substrate by thimet oligopeptidase. Overexpression of thimet oligopeptidase in both CHO-S and HEK293 cells was sufficient to reduce luciferase activation triggered by a specific GPCR agonist. Moreover, using individual peptides as baits in affinity columns, several proteins involved in GPCR signaling were identified, including alpha-adaptin A and dynamin 1. These results suggest that before their complete degradation, intracellular peptides similar to those generated by proteasomes can actively affect cell signaling, probably representing additional bioactive molecules within cells.
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Financiadora de Estudos e Projetos
National Laboratory of Synchrotron Light (São Paulo Proteome Network)
Número do financiamento FAPESP: 04/04933-2
Data 2008-09-05
Publicado em Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 283, n. 36, p. 24448-24459, 2008.
ISSN 0021-9258 (Sherpa/Romeo, fator de impacto)
Editor Amer Soc Biochemistry Molecular Biology Inc
Extensão 24448-24459
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000258820000020

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