Journal article

Extracellular matrix controls insulin signaling in mammary epithelial cells through the RhoA/Rok pathway

  • Lee, Yi-Ju Institute of Immunology, Chung Shan Medical University, Taichung, Taiwan
  • Hsu, Tsai-Ching Institute of Immunology, Chung Shan Medical University, Taichung, Taiwan
  • Du, Jyun-Yi Institute of Immunology, Chung Shan Medical University, Taichung, Taiwan
  • Valentijn, Anthony J. Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, UK
  • Wu, Tung-Yi Institute of Immunology, Chung Shan Medical University, Taichung, Taiwan
  • Cheng, Cheng-Fu Institute of Immunology, Chung Shan Medical University, Taichung, Taiwan
  • Yang, Zhihong Vascular Biology, Institute of Physiology, University of Fribourg, Switzerland
  • Streuli, Charles H. Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, UK
Show more…
    23.04.2009
Published in:
  • Journal of Cellular Physiology. - 2009, vol. 220, no. 2, p. 476-484
English Cellular responses are determined by a number of signaling cues in the local microenvironment, such as growth factors and extracellular matrix (ECM). In cultures of mammary epithelial cells (MECs), functional differentiation requires at least two types of signal, lactogenic hormones (i.e., prolactin, insulin, and hydrocortisone) and the specialized ECM, basement membrane (BM). Our previous work has shown that ECM affects insulin signaling in mammary cells. Cell adhesion to BM promotes insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and association of PI3K with IRS-1, whereas cells cultured on stromal ECM are inefficient in transducing these post-receptor events. Here we examine the mechanisms underlying ECM control of IRS phosphorylation. Compared to cells cultured on BM, cells on plastic exhibit higher level of RhoA activity. The amount and the activity of Rho kinase (Rok) associated with IRS-1 are greater in these cells, leading to serine phosphorylation of IRS-1. Expression of dominant negative RhoA and the application of Rok inhibitor Y27632 in cells cultured on plastic augment tyrosine phosphorylation of IRS-1. Conversely, expression of constitutively active RhoA in cells cultured on BM impedes insulin signaling. These data indicate that RhoA/Rok is involved in substratum-mediated regulation of insulin signaling in MECs, and under the conditions where proper adhesion to BM is missing, such as after wounding and during mammary gland involution, insulin-mediated cellular differentiation and survival would be defective.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/301228
Statistics

Document views: 6 File downloads:
  • yang_emc.pdf: 2