Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Curr Opin Cell Biol ; 51: 81-88, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29268141

RESUMO

The Hedgehog (Hh) pathway plays a central role in the development of multicellular organisms, guiding cell differentiation, proliferation and survival. While many components of the vertebrate pathway were discovered two decades ago, the mechanism by which the Hh signal is transmitted across the plasma membrane remains mysterious. This fundamental task in signalling is carried out by Smoothened (SMO), a human oncoprotein and validated cancer drug target that is a member of the G-protein coupled receptor protein family. Recent structural and functional studies have advanced our mechanistic understanding of SMO activation, revealing its unique regulation by two separable but allosterically-linked ligand-binding sites. Unexpectedly, these studies have nominated cellular cholesterol as having an instructive role in SMO signalling.


Assuntos
Proteínas de Drosophila/metabolismo , Proteínas Hedgehog/metabolismo , Vertebrados/metabolismo , Animais , Sítios de Ligação , Drosophila melanogaster , Humanos , Ligantes , Transdução de Sinais
2.
Elife ; 52016 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-27705744

RESUMO

Cholesterol is necessary for the function of many G-protein coupled receptors (GPCRs). We find that cholesterol is not just necessary but also sufficient to activate signaling by the Hedgehog (Hh) pathway, a prominent cell-cell communication system in development. Cholesterol influences Hh signaling by directly activating Smoothened (SMO), an orphan GPCR that transmits the Hh signal across the membrane in all animals. Unlike many GPCRs, which are regulated by cholesterol through their heptahelical transmembrane domains, SMO is activated by cholesterol through its extracellular cysteine-rich domain (CRD). Residues shown to mediate cholesterol binding to the CRD in a recent structural analysis also dictate SMO activation, both in response to cholesterol and to native Hh ligands. Our results show that cholesterol can initiate signaling from the cell surface by engaging the extracellular domain of a GPCR and suggest that SMO activity may be regulated by local changes in cholesterol abundance or accessibility.


Assuntos
Colesterol/metabolismo , Ouriços/metabolismo , Transdução de Sinais , Receptor Smoothened/agonistas , Animais , Linhagem Celular , Células Epiteliais/fisiologia , Fibroblastos/fisiologia , Humanos , Camundongos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...