Integrins activate trimeric G proteins via the nonreceptor protein GIV/Girdin.

ABSTRACT: Signal transduction via integrins and G protein-coupled receptors is critical to control cell behavior. These two receptor classes have been traditionally believed to trigger distinct and independent signaling cascades in response to extracellular cues. Here, we report a novel mechanism of integrin signaling that requires activation of the trimeric G protein Gαi by the nonreceptor guanine nucleotide exchange factor (GEF) GIV (also known as Girdin), a metastasis-associated protein. We demonstrate that GIV enhances integrin-dependent cell responses upon extracellular matrix stimulation and makes tumor cells more invasive. These responses include remodeling of the actin cytoskeleton and PI3K-dependent signaling, resulting in enhanced haptotaxis and invasion. We show that both GIV and its subs

SUBMITTER: Leyme A 

PROVIDER: S-EPMC4586755 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature