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PMID:14676278

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Citation

Zoubiane, GS, Valentijn, A, Lowe, ET, Akhtar, N, Bagley, S, Gilmore, AP and Streuli, CH (2004) A role for the cytoskeleton in prolactin-dependent mammary epithelial cell differentiation. J. Cell. Sci. 117:271-80

Abstract

The function of exocrine glands depends on signals within the extracellular environment. In the mammary gland, integrin-mediated adhesion to the extracellular matrix protein laminin co-operates with soluble factors such as prolactin to regulate tissue-specific gene expression. The mechanism of matrix and prolactin crosstalk and the activation of downstream signals are not fully understood. Because integrins organize the cytoskeleton, we analysed the contribution of the cytoskeleton to prolactin receptor activation and the resultant stimulation of milk protein gene expression. We show that the proximal signalling events initiated by prolactin (i.e. tyrosine phosphorylation of receptor and the associated kinase Jak2) do not depend on an intact actin cytoskeleton. However, actin networks and microtubules are both necessary for continued mammary cell differentiation, because cytoskeletal integrity is required to transduce the signals between prolactin receptor and Stat5, a transcription factor necessary for milk protein gene transcription. The two different cytoskeletal scaffolds regulate prolactin signalling through separate mechanisms that are specific to cellular differentiation but do not affect the general profile of protein synthesis.

Links

PubMed Online version:10.1242/jcs.00855

Keywords

Animals; Caseins/metabolism; Cell Differentiation/physiology; Cells, Cultured; Colchicine/pharmacology; Cytochalasin D/pharmacology; Cytoskeleton/drug effects; Cytoskeleton/metabolism; DNA-Binding Proteins/metabolism; Epithelial Cells/metabolism; Female; Immunohistochemistry; Integrins/metabolism; Janus Kinase 2; Mammary Glands, Animal/metabolism; Mice; Milk Proteins/metabolism; Nucleic Acid Synthesis Inhibitors/pharmacology; Phosphorylation; Pregnancy; Prolactin/metabolism; Protein-Tyrosine Kinases/metabolism; Proto-Oncogene Proteins; Receptors, Prolactin/metabolism; STAT5 Transcription Factor; Signal Transduction/physiology; Trans-Activators/metabolism; Transcription, Genetic; Tyrosine/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status


See also

References

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