title: A novel protein kinase D phosphorylation site in the tumor suppressor Rab interactor 1 is critical for coordination of cell migration.
abstract: 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.
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, 70569 Stuttgart, Germany Panatecs GmbH, 72070 Tübingen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Ziegler
authors.forename: Tim
authors.initials: T
authors.lastname: Eiseler
authors.forename: Rolf-Peter
authors.initials: RP
authors.lastname: Scholz
authors.forename: Alexander
authors.initials: A
authors.lastname: Beck
authors.forename: Gisela
authors.initials: G
authors.lastname: Link
authors.forename: Angelika
authors.initials: A
authors.lastname: Hausser
mesh_terms: D000199:Actins / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology; D002465:Cell Movement; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D000906:Antibodies; D047908:Intracellular Signaling Peptides and Proteins; C092117:RIN1 protein, human; D025521:Tumor Suppressor Proteins; D010768:Phosphoserine; C426236:ARG tyrosine kinase; C089212:protein kinase D; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C