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Content Provider | World Health Organization (WHO)-Global Index Medicus |
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Author | Schleicher, Michael Batsios, Petros Gagnon, Zachary Willard, Stacey S. Devreotes, Peter N. Rohlfs, Meino Sanséau, Doriane Lee, Josephine Borleis, Jane Artemenko, Yulia |
Description | Author Affiliation: Artemenko Y ( Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.); |
Abstract | Chemotaxis depends on a network of parallel pathways that coordinate cytoskeletal events to bias cell movement along a chemoattractant gradient. Using a forward genetic screen in Dictyostelium discoideum, we identified the Ste20 kinase KrsB, a homolog of tumor suppressors Hippo and MST1/2, as a negative regulator of cell spreading and substrate attachment. The excessive adhesion of krsB(-) cells reduced directional movement and prolonged the streaming phase of multicellular aggregation. These phenotypes depended on an intact kinase domain and phosphorylation of a conserved threonine (T176) within the activation loop. Chemoattractants triggered a rapid, transient autophosphorylation of T176 in a heterotrimeric G protein-dependent and PI3K- and TorC2-independent manner. The active phosphorylated form of KrsB acts to decrease adhesion to the substrate. Taken together these studies suggest that cycling between active and inactive forms of KrsB may provide the dynamic regulation of cell adhesion needed for proper cell migration and chemotaxis. KrsB interacts genetically with another D. discoideum Hippo/MST homolog, KrsA, but the two genes are not functionally redundant. These studies show that Hippo/MST proteins, like the tumor suppressor PTEN and oncogenes Ras and PI3K, play a key role in cell morphological events in addition to their role in regulating cell growth. |
ISSN | 00278424 |
e-ISSN | 10916490 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Issue Number | 34 |
Volume Number | 109 |
Language | English |
Publisher | National Academy of Sciences |
Publisher Date | 2012-08-01 |
Publisher Place | United States |
Access Restriction | Open |
Subject Keyword | Chemotaxis Gene Expression Regulation, Neoplastic Hepatocyte Growth Factor Physiology Proto-Oncogene Proteins Protozoan Proteins Genetics Animals Cell Adhesion Cell Movement Dictyostelium Dimerization Genes, Tumor Suppressor Green Fluorescent Proteins Chemistry Nerve Tissue Proteins Phosphatidylinositol 3-Kinases Metabolism Phosphorylation Protein-Serine-Threonine Kinases Threonine Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
Content Type | Text |
Resource Type | Article |
Subject | Multidisciplinary |
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