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Originally published online as doi:10.2353/ajpath.2009.080890 on April 6, 2009

Published online before print April 6, 2009
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(American Journal of Pathology. 2009;174:1756-1765.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080890

The Transmembrane src Substrate Trask Is an Epithelial Protein that Signals during Anchorage Deprivation

Danislav S. Spassov*, Frederick L. Baehner{dagger}, Ching Hang Wong*, Stephen McDonough* and Mark M. Moasser*

From the Departments of Medicine,* and Pathology,{dagger} University of California, San Francisco, San Francisco, California

The roles of epithelial cells encompass both cellular- and tissue-level functions that involve numerous cell–cell and cell–matrix interactions, which ultimately mediate the highly structured arrangement of cells on a basement membrane. Although maintaining this basic structure is critical for preserving tissue integrity, plasticity in epithelial cell behavior is also critical for processes such as cell migration during development or wound repair, mitotic cell detachment, and physiological shedding. The mechanisms that mediate epithelial cell plasticity are only beginning to be understood. We previously identified Trask, a transmembrane protein that is phosphorylated by src kinases during mitosis. In this study, we report that the phosphorylation of Trask is associated with anchorage loss in epithelial cells. Phosphorylation of Trask is seen during the cell-detachment phase of mitosis, in experimentally induced interphase detachment, and during cell migration in experimental epithelial models. An analysis of human tissues shows that Trask is widely expressed in many epithelial tissues but not in most tissues of mesenchymal origin, except for a subset of early hematopoietic cells. Trask is not phosphorylated in epithelial tissues in vivo; however, its phosphorylation is seen in epithelial cells undergoing mitosis or physiological shedding. Trask is a novel epithelial membrane protein that is phosphorylated by src kinases when epithelial cells disengage from their tissue framework, identifying an important new regulator of epithelial tissue dynamics.






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Copyright © 2009 by the American Society for Investigative Pathology.