A novel protein kinase D phosphorylation site in the tumor suppressor Rab interactor 1 is critical for coordination of cell migration
| Autor: | Susanne Ziegler, Rolf-Peter Scholz, Angelika Hausser, Tim Eiseler, Gisela Link, Alexander Beck |
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| Rok vydání: | 2011 |
| Předmět: |
inorganic chemicals
Amino Acid Motifs Molecular Sequence Data macromolecular substances Biology environment and public health Antibodies Phosphoserine chemistry.chemical_compound Cell Movement Humans Protein phosphorylation Amino Acid Sequence Phosphorylation Molecular Biology Protein Kinase C Protein kinase C Serine/threonine-specific protein kinase Kinase Tumor Suppressor Proteins Intracellular Signaling Peptides and Proteins Articles Cell Biology Protein-Tyrosine Kinases Molecular biology Actins Cell biology enzymes and coenzymes (carbohydrates) Protein Transport Cell Motility HEK293 Cells chemistry bacteria Rab Signal transduction Subcellular Fractions |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e10-05-0427 |
| Popis: | RIN1 is a regulator of epithelial cell migration. We identify serine 292 as a novel phosphorylation site for PKD in RIN1. Phosphorylation at this site controls RIN1-mediated inhibition of cell migration by modulating the direct activation of Abl kinases. The multifunctional signal adapter protein Ras and Rab interactor 1 (RIN1) is a Ras effector protein involved in the regulation of epithelial cell processes such as cell migration and endocytosis. RIN1 signals via two downstream pathways, namely the activation of Rab5 and Abl family kinases. Protein kinase D (PKD) phosphorylates RIN1 at serine 351 in vitro, thereby regulating interaction with 14–3-3 proteins. Here, we report the identification of serine 292 in RIN1 as an in vivo PKD phosphorylation site. PKD-mediated phosphorylation at this site was confirmed with a phospho-specific antibody and by mass spectrometry. We demonstrate that phosphorylation at serine 292 controls RIN1-mediated inhibition of cell migration by modulating the activation of Abl kinases. We further provide evidence that RIN1 in vivo phosphorylation at serine 351 occurs independently of PKD. Collectively, our data identify a novel PKD signaling pathway through RIN1 and Abl kinases that is involved in the regulation of actin remodeling and cell migration. |
| Databáze: | OpenAIRE |
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