PMID: 26985018    RLIMS-P  1    Check other iTextMine results Issue Report

Title

1.	Tension on JAM-A activates RhoA via GEF-H1 and p115 RhoGEF.

Abstract

2.	Junctional adhesion molecule A (JAM-A) is a broadly expressed adhesion molecule that regulates cell-cell contacts and facilitates leukocyte transendothelial migration.
3.	The latter occurs through interactions with the integrin LFA-1.
4.	Although we understand much about JAM-A, little is known regarding the protein's role in mechanotransduction or as a modulator of RhoA signaling.
5.	We found that tension imposed on JAM-A activates RhoA, which leads to increased cell stiffness.
6.	Activation of RhoA in this system depends on PI3K-mediated activation of GEF-H1 and p115 RhoGEF.
7.	These two GEFs are further regulated by FAK/ERK and Src family kinases, respectively.
8.	Finally, we show that phosphorylation of JAM-A at Ser-284 is required for RhoA activation in response to tension.
9.	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.

Entity: 2, Relation: 1  

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