Focal adhesions are foci for tyrosine-based signal transduction via GIV/Girdin and G proteins.
Focal adhesions are foci for tyrosine-based signal transduction via GIV/Girdin and G proteins.
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DOI：
10.1091/mbc.e15-07-0496
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发表时间：
2015-12-01
影响因子：
3.3
通讯作者：
Ghosh P
中科院分区：
文献类型：
--
作者：
Lopez-Sanchez I;Kalogriopoulos N;Lo IC;Kabir F;Midde KK;Wang H;Ghosh P
GIV is a guanine-nucleotide exchange factor and a bona fide metastasis-related protein. It is found, unexpectedly, that focal adhesions are the major foci for GIV-dependent signaling and that GIV modulates integrin-FAK signaling via activation of G proteins. It is also shown how this phenomenon is altered during cancer progression. GIV/Girdin is a multimodular signal transducer and a bona fide metastasis-related protein. As a guanidine exchange factor (GEF), GIV modulates signals initiated by growth factors (chemical signals) by activating the G protein Gαi. Here we report that mechanical signals triggered by the extracellular matrix (ECM) also converge on GIV-GEF via β1 integrins and that focal adhesions (FAs) serve as the major hubs for mechanochemical signaling via GIV. GIV interacts with focal adhesion kinase (FAK) and ligand-activated β1 integrins. Phosphorylation of GIV by FAK enhances PI3K-Akt signaling, the integrity of FAs, increases cell–ECM adhesion, and triggers ECM-induced cell motility. Activation of Gαi by GIV-GEF further potentiates FAK-GIV-PI3K-Akt signaling at the FAs. Spatially restricted signaling via tyrosine phosphorylated GIV at the FAs is enhanced during cancer metastasis. Thus GIV-GEF serves as a unifying platform for integration and amplification of adhesion (mechanical) and growth factor (chemical) signals during cancer progression.
