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Adaptation of cAMP signaling system in SH-SY5Y neuroblastoma cells following expression of a constitutively active stimulatory G protein alpha, Q227L Gsalpha
Experimental & Molecular Medicine ; : 37-45, 2001.
Artículo en Inglés | WPRIM | ID: wpr-31943
ABSTRACT
Heterotrimeric GTP-binding proteins (G protein) are known to participate in the transduction of signals from ligand activated receptors to effector molecules to elicit cellular responses. Sustained activation of cAMP-G protein signaling system by agonist results in desensitization of the pathway at receptor levels, however it is not clear whether such receptor responses induce other changes in post-receptor signaling path that are associated with maintenance of AMP levels, i.e. cAMP-forming adenylate cyclase (AC), cAMP-degrading cyclic nucleotide phosphodiesterase (PDE) and cAMP-dependent protein kinase (PKA). Experiments were performed to determine the expression of AC, PDE, and PKA isoforms in SH-SY5Y neuroblastoma cells, in which cAMP system was activated by expressing a constitutively activated mutant of stimulatory G protein (Q227L Gsalpha). Expression of ACI mRNA was increased, but levels of ACVIII and ACIX mRNA were decreased. All of the 4 expressed isoforms of PDE (PDE1C, PDE2, PDE 4A, and PDE4B) were increased in mRNA expression; the levels of PKA RIalpha, RIbeta, and RIIbeta were increased moderately, however, those of RIIalpha and Calpha were increased remarkably. The activities of AC, PDE and PKA were also increased in the SH-SY5Y cells expressing Q227L Gsalpha. The similar changes in expression and activity of AC, PDE and PKA were observed in the SH-SY5Y cells treated with dbcAMP for 6 days. Consequently, it is concluded that the cAMP system adapts at the post-receptor level to a sustained activation of the system by differential expression of the isoforms of AC, PDE, and PKA in SH-SY5Y neuroblastoma. We also showed that an increase in cellular cAMP concentration might mediate the observed changes in the cAMP system.
Asunto(s)

Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Células Tumorales Cultivadas / Transducción de Señal / Adenilil Ciclasas / Proteínas Quinasas Dependientes de AMP Cíclico / AMP Cíclico / 3',5'-AMP Cíclico Fosfodiesterasas / Subunidades alfa de la Proteína de Unión al GTP Gs / Proteínas de Unión al GTP Heterotriméricas / Isoenzimas / Isoproterenol Límite: Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2001 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Células Tumorales Cultivadas / Transducción de Señal / Adenilil Ciclasas / Proteínas Quinasas Dependientes de AMP Cíclico / AMP Cíclico / 3',5'-AMP Cíclico Fosfodiesterasas / Subunidades alfa de la Proteína de Unión al GTP Gs / Proteínas de Unión al GTP Heterotriméricas / Isoenzimas / Isoproterenol Límite: Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2001 Tipo del documento: Artículo