ArticleThe Journal of biological chemistry2008
Intramolecular activation mechanism of the Dictyostelium LRRK2 homolog Roco protein GbpC.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Diverse Roles of the Multiple Phosphodiesterases in the Regulation of Cyclic Nucleotide Signaling inCells · 2025Review
- Exon shuffling and alternative splicing of ROCO genes in brown algae enables a diverse repertoire of candidate immune receptors.Frontiers in plant science · 2024Article
- Roc, the G-domain of the Parkinson's disease-associated protein LRRK2.Trends in biochemical sciences · 2022Review
- Roco Proteins and the Parkinson's Disease-Associated LRRK2.International journal of molecular sciences · 2018Review
- Partial genetic suppression of a loss-of-function mutant of the neuronal ceroid lipofuscinosis-associated protease TPP1 in Dictyostelium discoideum.Disease models & mechanisms · 2015Article
- Genetic, structural, and molecular insights into the function of ras of complex proteins domains.Chemistry & biology · 2014Review
- Loss of Cln3 function in the social amoeba Dictyostelium discoideum causes pleiotropic effects that are rescued by human CLN3.PloS one · 2014Article
- Association between G2385R and R1628P polymorphism of LRRK2 gene and sporadic Parkinson's disease in a Han-Chinese population in south-eastern China.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2013Article
- Roco kinase structures give insights into the mechanism of Parkinson disease-related leucine-rich-repeat kinase 2 mutations.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Multiple regulatory mechanisms for the Dictyostelium Roco protein GbpC.The Journal of biological chemistry · 2012Article
- The LRRK2-related Roco kinase Roco2 is regulated by Rab1A and controls the actin cytoskeleton.Molecular biology of the cell · 2011Article
- Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice.Neurobiology of disease · 2011Article
- Comparative genomics of the social amoebae Dictyostelium discoideum and Dictyostelium purpureum.Genome biology · 2011Article
- Impaired dopaminergic neurotransmission and microtubule-associated protein tau alterations in human LRRK2 transgenic mice.Neurobiology of disease · 2010Article
- ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2.PloS one · 2010Article
- The ROCO kinase QkgA is necessary for proliferation inhibition by autocrine signals in Dictyostelium discoideum.Eukaryotic cell · 2010Article
- Characterization of the Roco protein family in Dictyostelium discoideum.Eukaryotic cell · 2010Article
- Dual regulation of a Dictyostelium STAT by cGMP and Ca2+ signalling.Journal of cell science · 2010Article
- Eukaryotic chemotaxis: a network of signaling pathways controls motility, directional sensing, and polarity.Annual review of biophysics · 2010Review
- The WD40 domain is required for LRRK2 neurotoxicity.PloS one · 2009Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GbpC is a large multidomain protein involved in cGMP-mediated chemotaxis in the cellular slime mold Dictyostelium discoideum. GbpC belongs to the Roco family of proteins that often share a central core region, consisting of leucine-rich repeats, a Ras domain (Roc), a Cor domain, and a MAPKKKinase domain. In addition to this core, GbpC contains a RasGEF domain and two cGMP-binding domains. Here, we report on an intramolecular signaling cascade of GbpC. In vitro, the RasGEF domain of GbpC specifically accelerates the GDP/GTP exchange of the Roc domain. Moreover, cGMP binding to GbpC strongly stimulates the binding of GbpC to GTP-agarose, suggesting cGMP-stimulated GDP/GTP exchange at the Roc domain. The function of the protein in vivo was investigated by rescue analysis of the chemotactic defect of gbpC null cells. Mutants that lack a functional guanine exchange factor (GEF), Roc, or kinase domain are inactive in vivo. Together, the results suggest a four-step intramolecular activation mechanism of the Roco protein GbpC: cGMP binding to the cyclic nucleotide-binding domains, activation of the GEF domain, GDP/GTP exchange of Roc, and activation of the MAPKKK domain.
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