Rac1 links integrin-mediated adhesion to the control of lactational differentiation in mammary epithelia.
J Cell Biol
; 173(5): 781-93, 2006 Jun 05.
Article
en En
| MEDLINE
| ID: mdl-16754961
ABSTRACT
The expression of tissue-specific genes during mammary gland differentiation relies on the coincidence of two distinct signaling events the continued engagement of beta1 integrins with the extracellular matrix (ECM) and a hormonal stimulus from prolactin (Prl). How the integrin and Prl receptor (PrlR) systems integrate to regulate milk protein gene synthesis is unknown. In this study, we identify Rac1 as a key link. Dominant-negative Rac1 prevents Prl-induced synthesis of the milk protein beta-casein in primary mammary epithelial cells cultured as three-dimensional acini on basement membrane. Conversely, activated Rac1 rescues the defective beta-casein synthesis that occurs under conditions not normally permissive for mammary differentiation, either in beta1 integrin-null cells or in wild-type cells cultured on collagen. Rac1 is required downstream of integrins for activation of the PrlR/Stat5 signaling cascade. Cdc42 is also necessary for milk protein synthesis but functions via a distinct mechanism to Rac1. This study identifies the integration of signals provided by ECM and hormones as a novel role for Rho family guanosine triphosphatases.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neuropéptidos
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Lactancia
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Integrina beta1
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Proteínas de Unión al GTP rac
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Células Epiteliales
Límite:
Animals
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Pregnancy
Idioma:
En
Año:
2006
Tipo del documento:
Article