Submitted on March 6, 2009
Revised on June 11, 2009
Accepted on July 1, 2009
Mechanical stretch decreases FAK phosphorylation and reduces cell migration through loss of JIP3-induced JNK phosphorylation in airway epithelial cells
Leena P. Desai1, Steven R. White2, and Christopher M. Waters3*
1 University of Tennessee Health Science Center
2 University of Chicago
3 University of Tennessee-Memphis
* To whom correspondence should be addressed. E-mail: cwaters2{at}utmem.edu.
c-Jun-NH2-terminal kinase (JNK) is a non-receptor kinase involved in the early events that signal cell migration after injury. However, the linkage to early signals required to initiate the migration response to JNK has not been defined in airway epithelial cells, which exist in an envi-ronment subjected to cyclic mechanical strain (MS). The present studies demonstrate that the JNK/stress activated protein kinase associated protein 1 (JSAP1) (also termed JNK interacting protein 3, JIP3), a scaffold factor for mitogen-activated protein kinase (MAPK) cascades that links JNK activation to focal adhesion kinase (FAK), are both associated and activated following mechanical injury in 16HBE14o- airway epithelial cells, and that both FAK and JIP3 phosphorylation seen after injury are decreased in cells subjected to cyclic MS. Over-expression of either WT-FAK or WT-JIP3 enhanced phosphorylation and kinase activation of JNK and reduced the inhibitory ef-fect of cyclic MS. These results suggest that cyclic MS impairs signaling of cell migration after injury via a pathway that involves FAK-JIP3-JNK.
