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Thrombin stimulated glioblastoma cell adhesion is mediated by Rap1 and integrin activation
Author(s) -
Sayyah Jacqueline,
Stupack Dwayne,
Brown Joan Heller
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.664.8
Subject(s) - rap1 , microbiology and biotechnology , integrin , rhoa , cell adhesion , thrombin , signal transduction , chemistry , biology , cell , biochemistry , immunology , platelet
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.