Distinct forms of the protein kinase-dependent activator of tyrosine and tryptophan hydroxylases.
J Mol Biol
; 217(1): 125-32, 1991 Jan 05.
Article
em En
| MEDLINE
| ID: mdl-1671102
ABSTRACT
Tyrosine and tryptophan hydroxylases are the key enzymes in the regulation of catecholamine and serotonin levels in neurons and other endocrine cells. Among the mechanisms proposed for the modulation of activity, phosphorylation of the enzyme is believed to be of functional significance with respect to the stimulus-response coupling, but the precise mechanism is unknown. Here, we show the existence of multiple, distinct forms of the 14-3-3 activator protein, a neuronal protein essential for activation of tyrosine and tryptophan hydroxylases by Ca2+/calmodulin-dependent protein kinase type II. Bovine brain 14-3-3 protein was resolved by reversed-phase chromatography into seven polypeptides (alpha to eta), all of which were active towards tryptophan hydroxylase when the renatured preparations were assayed in the presence of Ca2+, calmodulin and the protein kinase. Determination of the amino acid sequences of the beta and gamma chains and comparison of the sequences with the previously determined sequence of the eta chain revealed that these molecules are highly homologous, and share a common structural feature in containing an extremely acidic C-terminal region predicted as a domain for interaction with the phosphorylated hydroxylases. Northern blot analysis indicated that the beta, gamma and eta chain are expressed abundantly in the brain; however, these polypeptides appear to be expressed with different tissue specificities because gamma mRNA is found only in the brain, while lower levels of beta and eta mRNAs are detected in several other tissues. These findings suggest the involvement of a diverse family of the activator protein in the stimulus-coupled, Ca2(+)-dependent regulation of monoamine biosynthesis.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Triptofano Hidroxilase
/
Tirosina 3-Mono-Oxigenase
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Mol Biol
Ano de publicação:
1991
Tipo de documento:
Article
País de afiliação:
Japão