Tension on JAM-A activates RhoA via GEF-H1 and p115 RhoGEF |
| |
| Authors: | David W Scott Caitlin E Tolbert Keith Burridge |
| |
| Institution: | University of Queensland;aDepartment of Cell Biology and Physiology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;bMcAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 |
| |
| Abstract: | Junctional adhesion molecule A (JAM-A) is a broadly expressed adhesion molecule that regulates cell–cell contacts and facilitates leukocyte transendothelial migration. The latter occurs through interactions with the integrin LFA-1. Although we understand much about JAM-A, little is known regarding the protein’s role in mechanotransduction or as a modulator of RhoA signaling. We found that tension imposed on JAM-A activates RhoA, which leads to increased cell stiffness. Activation of RhoA in this system depends on PI3K-mediated activation of GEF-H1 and p115 RhoGEF. These two GEFs are further regulated by FAK/ERK and Src family kinases, respectively. Finally, we show that phosphorylation of JAM-A at Ser-284 is required for RhoA activation in response to tension. These data demonstrate a direct role of JAM-A in mechanosignaling and control of RhoA and implicate Src family kinases in the regulation of p115 RhoGEF. |
| |
| Keywords: | |
|
|
