Isoform-Specific Phosphorylation in Human Hsp90ß Affects Interaction with Clients and the Cochaperone Cdc37.
J Mol Biol
; 429(5): 732-752, 2017 03 10.
Article
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| MEDLINE
| ID: mdl-28109840
ABSTRACT
The 90-kDa heat shock proteins (Hsp90s) assist the maturation of many key regulators of signal transduction pathways and cellular control circuits like protein kinases and transcription factors and chaperone their stability and activity. In this function, Hsp90s cooperate with some 30 cochaperones and they are themselves subject to regulation by numerous post-translational modifications. In vertebrates, two major isoforms exist in the cytosol, Hsp90α and Hsp90ß, which share a high degree of sequence identity and are expressed in tissue- and environmental condition-dependent manner. We identified an isoform-specific phosphorylation site in human Hsp90ß. This phosphorylation site seems to be linked to vertebrate evolution since it is not found in invertebrata but in all tetrapoda and many but not all fish species. We provide data suggesting that this phosphorylation is important for the activation of Hsp90 clients like glucocorticoid receptor and a protein kinase. Replacement of the phosphorylation site by glutamate affects the conformational dynamics of Hsp90 and interaction with the kinase-specific cochaperone Cdc37.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas HSP90 de Choque Térmico
/
Chaperoninas
/
Proteínas de Ciclo Celular
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Mol Biol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Alemania