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

被引:22
作者
Zucchi, I
Prinetti, A
Scotti, M
Valsecchi, V
Valaperta, R
Mento, E
Reinbold, R
Vezzoni, P
Sonnino, S
Albertini, A
Dulbecco, R
机构
[1] CNR, ITB, I-20090 Segrate, Italy
[2] Univ Milan, Dept Med Chem Biochem & Biotechnol, Study Ctr Funct Biochem Brain Lipids, I-20090 Segrate, Italy
[3] Univ Penn, Germline Dev Grp, Kennett Sq, PA 19348 USA
[4] Salk Inst Biol Studies, La Jolla, CA 92037 USA
关键词
D O I
10.1073/pnas.0307292101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页码:1880 / 1885
页数:6
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