Cell adhesion to the extracellular matrix (ECM) can activate signaling via focal adhesion kinase (FAK) leading to dynamic regulation of cellular morphology. Mechanistic basis for the lack of effective intracellular signaling by non-attached epithelial cells is poorly understood. To examine whether signaling in suspended cells is regulated by Fer cytoplasmic tyrosine kinase, we investigated the effect of ectopic Fer expression on signaling in suspended or adherent hepatocytes. We found that ectopic Fer expression in Huh7 hepatocytes in suspension or on non-permissive poly-lysine caused significant phosphorylation of FAK Tyr577, Tyr861, or Tyr925, but not Tyr397 or Tyr576. Fer-mediated FAK phosphorylation in suspended cells was independent of c-Src activity or growth factor stimulation, but dependent of cortactin expression. Consistent with these results, complex formation between FAK, Fer, and cortactin was observed in suspended cells. The Fer-mediated effect correlated with multiple membrane protrusions, even on poly-lysine. Together, these observations suggest that Fer may allow a bypass of anchorage-dependency for intracellular signal transduction in hepatocytes.
|Number of pages||11|
|Journal||Biochimica et Biophysica Acta - Molecular Cell Research|
|State||Published - May 2009|
Bibliographical noteFunding Information:
This work was supported by the grant funded by the Korea government [Research Programs for CPMRC, R13-2007-019-00000-0 from Korea Ministry of Education, Science and Technology to S-H Kim, New Drug Target Discovery, 2007-03536, and Cell Dynamic Research Center, R11-2007-007-01004-0 to J.W. Lee] and in part by research grant from Cancer Research Institute, Seoul National University (2007, to J.W. Lee).
- Cell adhesion
- Focal adhesion kinase
- Protein-protein interaction