ArticleMolecular and cellular biology2010
Regulation of the Rho family small GTPase Wrch-1/RhoU by C-terminal tyrosine phosphorylation requires Src.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- From disorder comes function: Regulation of small GTPase function by intrinsically disordered lipidated membrane anchor.Current opinion in structural biology · 2024Review
- Atypical RhoUV GTPases in development and disease.Biochemical Society transactions · 2024Review
- Molecular basis and current insights of atypical Rho small GTPase in cancer.Molecular biology reports · 2024Review
- RhoU forms homo-oligomers to regulate cellular responses.Journal of cell science · 2024Article
- Article
- The Arabidopsis Rho of Plants GTPase ROP1 Is a Potential Calcium-Dependent Protein Kinase (CDPK) Substrate.Plants (Basel, Switzerland) · 2021Article
- Fast-cycling Rho GTPases.Small GTPases · 2020Review
- Dysregulation of Rho GTPases in Human Cancers.Cancers · 2020Review
- Regulation and functions of RhoU and RhoV.Small GTPases · 2020Review
- The Atypical Rho GTPase CHW-1 Works with SAX-3/Robo To Mediate Axon Guidance inG3 (Bethesda, Md.) · 2018Article
- Rho GTPases, their post-translational modifications, disease-associated mutations and pharmacological inhibitors.Small GTPases · 2018Review
- Rho GTPases: Regulation and roles in cancer cell biology.Small GTPases · 2016Review
- Regulating Rho GTPases and their regulators.Nature reviews. Molecular cell biology · 2016Review
- Atypical RhoV and RhoU GTPases control development of the neural crest.Small GTPases · 2015Review
- Redox regulation of Rac1 by thiol oxidation.Free radical biology & medicine · 2015Article
- The C. elegans Chp/Wrch Ortholog CHW-1 Contributes to LIN-18/Ryk and LIN-17/Frizzled Signaling in Cell Polarity.PloS one · 2015Article
- Cellular expression profile of RhoA in rats with spinal cord injury.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2014Article
- The Role of Ect2 Nuclear RhoGEF Activity in Ovarian Cancer Cell Transformation.Genes & cancer · 2013Article
- Negative regulation of the RalGAP complex by 14-3-3.The Journal of biological chemistry · 2013Article
- Atypical RhoV and RhoU GTPases control development of the neural crest.Small GTPases · 2011Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Wrch-1 is an atypical Rho family small GTPase with roles in migration, epithelial cell morphogenesis, osteoclastogenesis, and oncogenic transformation. Here, we observed rapid relocalization of Wrch-1 from the plasma membrane upon serum stimulation. Studies revealed a requirement for serum-stimulated tyrosine phosphorylation of Wrch-1 at residue Y254 within its C-terminal membrane targeting domain, mediated by the nonreceptor tyrosine kinase Src. Genetic or pharmacological loss of Src kinase activity blocked both phosphorylation and relocalization of Wrch-1. Functionally, Y254 was required for proper Wrch-1 modulation of cystogenesis in three-dimensional culture, and the phospho-deficient mutant, Y254F, was enhanced in Wrch-1-mediated anchorage-independent growth. Mechanistically, C-terminal tyrosine phosphorylation and subsequent relocalization of Wrch-1 downregulated its ability to interact with and activate its effectors by decreasing active Wrch-1-GTP, perhaps by altering proximity to a GEF or GAP. Phospho-deficient Wrch-1(Y254F) remained at the plasma membrane and GTP bound and continued to recruit and activate its effector PAK, even upon serum stimulation. In contrast, a phospho-mimetic mutant, Y254E, was constitutively endosomally localized and GDP bound and failed to recruit PAK unless mutated to be constitutively active/GAP insensitive. C-terminal tyrosine phosphorylation thus represents a new paradigm in posttranslational control of small GTPase localization, activation, and biological function.
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Registered trials
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