Abstract
Rap1 is a Ras family GTPase that plays an important role in ERK1/2 activation, cell proliferation and adhesion. Little is known about the mechanisms for activation or the role of Rap1 in signaling through GPCRs. We have previously reported that thrombin coupling to the G protein‐coupled receptor PAR‐1 induces a robust and sustained increase in Rap1 activation that is mediated by RhoA‐phospholipase D (PLD) signaling and that this pathway is necessary for sustained ERK1/2 activation and glioblastoma cell proliferation. Rap1 also mediates cellular signals that regulate integrins from inside the cell thereby affecting integrin‐mediated cell adhesion. Accordingly, we asked whether PLD and Rap1 are critical for thrombin induced glioblastoma cell adhesion. Down‐regulation of PLD1 and Rap1 with siRNA significantly blocked thrombin induced glioblastoma cell adhesion to fibronectin by 50–60 percent. In addition, blocking β1 integrin activation via neutralizing antibody inhibited thrombin stimulated ERK1/2 activation in these cells. Collectively, our results suggest that Rap1 activation by thrombin contributes to integrin activation and downstream signaling that could be important for the aberrant growth or migration of glioblastoma cells. We are currently examining in more detail the integrin signaling pathways that are activated downstream of thrombin/PAR‐1 mediated Rap1 activation.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.