Sci. Signal., 23 August 2011
Defining a Migratory RouteThe serine-threonine kinase Tpl2, a mitogen-activated protein kinase kinase kinase, transduces signals from various plasma membrane receptors and has been implicated in pathways contributing to cancer and inflammation. Building on their earlier work showing that Tpl2 promotes cell migration in response to thrombin activation of the G protein–coupled receptor (GPCR) PAR1, Hatziapostolou et al. now define the signaling pathways through which this occurs. They found that PAR1 coupled to Gαi2 to activate Tpl2 and implicated the subsequent activation of phospholipase C–β3, production of inositol 1,4,5-trisphosphate, and cytoplasmic calcium signals in the migratory response. Moreover, they showed that Tpl2 mediated migratory signals through activation of several receptors other than PAR1. Their data contribute to our understanding of the pathways through which GPCRs and other receptors promote cell migration and may be pertinent to the mechanisms whereby Tpl2 contributes to cancer and inflammation.
Citation: M. Hatziapostolou, G. Koukos, C. Polytarchou, F. Kottakis, O. Serebrennikova, A. Kuliopulos, P. N. Tsichlis, Tumor Progression Locus 2 Mediates Signal-Induced Increases in Cytoplasmic Calcium and Cell Migration. Sci. Signal. 4, ra55 (2011).
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