Association of rat8 with Fyn protein kinase via lipid rafts is required for rat mammary cell differentiation in vitro

I. Zucchi, A. Prinetti, M. Scotti, V. Valsecchi, R. Valaperta, E. Mento, R. Reinbold, P. Vezzoni, S. Sonnino, A. Albertini, R. Dulbecco

Research output: Contribution to journalArticle

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Abstract

We previously identified rat8 in the pathway involved in epithelial cell differentiation that occurs in the rat mammary gland at pregnancy when tubules and alveoli are formed. rat8, which encodes an IFN-inducible membrane protein, is the rat homologue of the mouse gene fragilis. By differential detergent extraction and isopycnic sucrose density gradients, we show that rat8 protein is associated to lipid membrane domains together with Lyn and Fyn, members of the Src tyrosine kinase family. We also show that recruitment of rat8 to lipid membrane domains is a necessary step in mammary epithelial cell differentiation. Immunoprecipitation analysis, performed with an anti-Fyn protein antibody, shows that rat8 was present in the Fyn immunoprecipitate. Antisense oligonucleotides, used to inhibit Fyn protein expression, block mammary cell differentiation. Taken together, these results suggest that the functional interaction, via lipid membrane domains, of rat8 and Fyn proteins is required for mammary cell differentiation. Therefore, rat8, like fragilis, may be involved in developmental decisions and the demarcation of a subset of cells in the mammary gland that cause epithelial cells to develop into a network of tubuloalveolar structures involved in secretion.

Original languageEnglish
Pages (from-to)1880-1885
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number7
DOIs
Publication statusPublished - Feb 17 2004

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Protein Kinases
Cell Differentiation
Breast
Membrane Lipids
Lipids
Epithelial Cells
Human Mammary Glands
Proteins
src-Family Kinases
Antisense Oligonucleotides
Immunoprecipitation
Detergents
Sucrose
Membrane Proteins
Pregnancy
In Vitro Techniques
Antibodies
Genes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Association of rat8 with Fyn protein kinase via lipid rafts is required for rat mammary cell differentiation in vitro. / Zucchi, I.; Prinetti, A.; Scotti, M.; Valsecchi, V.; Valaperta, R.; Mento, E.; Reinbold, R.; Vezzoni, P.; Sonnino, S.; Albertini, A.; Dulbecco, R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 7, 17.02.2004, p. 1880-1885.

Research output: Contribution to journalArticle

Zucchi, I. ; Prinetti, A. ; Scotti, M. ; Valsecchi, V. ; Valaperta, R. ; Mento, E. ; Reinbold, R. ; Vezzoni, P. ; Sonnino, S. ; Albertini, A. ; Dulbecco, R. / Association of rat8 with Fyn protein kinase via lipid rafts is required for rat mammary cell differentiation in vitro. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 7. pp. 1880-1885.
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AU - Mento, E.

AU - Reinbold, R.

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AU - Dulbecco, R.

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