Focal adhesions are foci for tyrosine-based signal transduction via GIV/Girdin and G proteins
| Autor: | Krishna Midde, Nicholas A. Kalogriopoulos, Firooz Kabir, Pradipta Ghosh, I-Chung Lo, Inmaculada Lopez-Sanchez, Hong-Hui Wang |
|---|---|
| Přispěvatelé: | Weaver, Valerie Marie |
| Rok vydání: | 2015 |
| Předmět: |
G protein
medicine.medical_treatment Vesicular Transport Proteins GTP-Binding Protein alpha Subunits Gi-Go Biology Gi-Go Medical and Health Sciences Cell Line Focal adhesion Extracellular matrix 03 medical and health sciences Phosphatidylinositol 3-Kinases 0302 clinical medicine GTP-binding protein regulators GTP-Binding Proteins Cell Movement Cell Line Tumor medicine Animals Humans Guanine Nucleotide Exchange Factors Amino Acid Sequence Phosphorylation Molecular Biology 030304 developmental biology Cancer 0303 health sciences Focal Adhesions Tumor Brief Report Growth factor Microfilament Proteins Cell Biology Biological Sciences GTP-Binding Protein alpha Subunits 3. Good health Cell biology Hela Cells Focal Adhesion Kinase 1 COS Cells Tyrosine Guanine nucleotide exchange factor Signal transduction 030217 neurology & neurosurgery HeLa Cells Signal Transduction Protein Binding Developmental Biology |
| Zdroj: | Molecular biology of the cell, vol 26, iss 24 Molecular Biology of the Cell |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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