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The role of (auto)-phosphorylation in the complex activation mechanism of LRRK2.
Athanasopoulos PS, Heumann R, Kortholt A. Athanasopoulos PS, et al. Among authors: kortholt a. Biol Chem. 2018 Jun 27;399(7):643-647. doi: 10.1515/hsz-2017-0332. Biol Chem. 2018. PMID: 29537215 Review.
DdPDE4, a novel cAMP-specific phosphodiesterase at the surface of dictyostelium cells.
Bader S, Kortholt A, Snippe H, Van Haastert PJ. Bader S, et al. Among authors: kortholt a. J Biol Chem. 2006 Jul 21;281(29):20018-26. doi: 10.1074/jbc.M600040200. Epub 2006 Apr 27. J Biol Chem. 2006. PMID: 16644729
The deduced amino acid sequence predicts that DdPDE4 has a leader sequence, two transmembrane segments, and an extracellular catalytic domain that exhibits a high degree of homology with human cAMP-specific PDE8. Expression of the catalytic domain of DdPDE4 shows th …
The deduced amino acid sequence predicts that DdPDE4 has a leader sequence, two transmembrane segments, and an extracellular catalyti …
Characterization of the GbpD-activated Rap1 pathway regulating adhesion and cell polarity in Dictyostelium discoideum.
Kortholt A, Rehmann H, Kae H, Bosgraaf L, Keizer-Gunnink I, Weeks G, Wittinghofer A, Van Haastert PJ. Kortholt A, et al. J Biol Chem. 2006 Aug 18;281(33):23367-76. doi: 10.1074/jbc.M600804200. Epub 2006 Jun 12. J Biol Chem. 2006. PMID: 16769729
GbpD, a putative nucleotide exchange factor for small G-proteins of the Ras family, has been implicated in adhesion, cell polarity, and chemotaxis in Dictyostelium. ...Phg2, a serine/threonine-specific kinase, directly interacts with Rap1 via its Ras association dom …
GbpD, a putative nucleotide exchange factor for small G-proteins of the Ras family, has been implicated in adhesion, cell polarity, a …
Regulation of phagocytosis in Dictyostelium by the inositol 5-phosphatase OCRL homolog Dd5P4.
Loovers HM, Kortholt A, de Groote H, Whitty L, Nussbaum RL, van Haastert PJ. Loovers HM, et al. Among authors: kortholt a. Traffic. 2007 May;8(5):618-28. doi: 10.1111/j.1600-0854.2007.00546.x. Epub 2007 Mar 2. Traffic. 2007. PMID: 17343681
Dd5P4 is the Dictyostelium homolog of human OCRL (oculocerebrorenal syndrome of Lowe); both have a RhoGAP domain and a 5-phosphatase domain that acts on phosphatidylinositol 4,5-bisphosphate/phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3). ...In dd5p4-null ce …
Dd5P4 is the Dictyostelium homolog of human OCRL (oculocerebrorenal syndrome of Lowe); both have a RhoGAP domain and a 5-phosp …
Structure of the Roc-COR domain tandem of C. tepidum, a prokaryotic homologue of the human LRRK2 Parkinson kinase.
Gotthardt K, Weyand M, Kortholt A, Van Haastert PJ, Wittinghofer A. Gotthardt K, et al. Among authors: kortholt a. EMBO J. 2008 Aug 20;27(16):2239-49. doi: 10.1038/emboj.2008.150. Epub 2008 Jul 24. EMBO J. 2008. PMID: 18650931 Free PMC article.
We show that Roc is highly homologous to Ras, whereas the COR domain is a dimerisation device. The juxtaposition of the G-domains and mutational analysis suggest that the Roc GTPase reaction is stimulated and/or regulated by dimerisation in a nucleotide-dependent ma …
We show that Roc is highly homologous to Ras, whereas the COR domain is a dimerisation device. The juxtaposition of the G-domains and …
Intramolecular activation mechanism of the Dictyostelium LRRK2 homolog Roco protein GbpC.
van Egmond WN, Kortholt A, Plak K, Bosgraaf L, Bosgraaf S, Keizer-Gunnink I, van Haastert PJ. van Egmond WN, et al. Among authors: kortholt a. J Biol Chem. 2008 Oct 31;283(44):30412-20. doi: 10.1074/jbc.M804265200. Epub 2008 Aug 14. J Biol Chem. 2008. PMID: 18703517 Free PMC article.
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 …
GbpC is a large multidomain protein involved in cGMP-mediated chemotaxis in the cellular slime mold Dictyostelium discoideum. GbpC be …
Multiple regulatory mechanisms for the Dictyostelium Roco protein GbpC.
Kortholt A, van Egmond WN, Plak K, Bosgraaf L, Keizer-Gunnink I, van Haastert PJ. Kortholt A, et al. J Biol Chem. 2012 Jan 20;287(4):2749-58. doi: 10.1074/jbc.M111.315739. Epub 2011 Nov 26. J Biol Chem. 2012. PMID: 22119747 Free PMC article.
GbpC is a multidomain Roco protein in Dictyostelium, involved in transduction of intracellular cGMP that is produced by chemotactic signals. ...Together, the results show that GbpC receives multiple input signals that are both required for functional activity in vivo. cAMP …
GbpC is a multidomain Roco protein in Dictyostelium, involved in transduction of intracellular cGMP that is produced by chemotactic s …
Roco kinase structures give insights into the mechanism of Parkinson disease-related leucine-rich-repeat kinase 2 mutations.
Gilsbach BK, Ho FY, Vetter IR, van Haastert PJ, Wittinghofer A, Kortholt A. Gilsbach BK, et al. Among authors: kortholt a. Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10322-7. doi: 10.1073/pnas.1203223109. Epub 2012 Jun 11. Proc Natl Acad Sci U S A. 2012. PMID: 22689969 Free PMC article.
Here we show that Dictyostelium discoideum Roco4 is a suitable model to study the structural and biochemical characteristics of the LRRK2 kinase and can be used for optimization of current and identification of new LRRK2 inhibitors. ...
Here we show that Dictyostelium discoideum Roco4 is a suitable model to study the structural and biochemical characteristics of the L …
Structural biology of the LRRK2 GTPase and kinase domains: implications for regulation.
Gilsbach BK, Kortholt A. Gilsbach BK, et al. Among authors: kortholt a. Front Mol Neurosci. 2014 May 5;7:32. doi: 10.3389/fnmol.2014.00032. eCollection 2014. Front Mol Neurosci. 2014. PMID: 24847205 Free PMC article. Review.
Human leucine rich repeat kinase 2 (LRRK2) belongs to the Roco family of proteins, which are characterized by the presence of a Ras-like G-domain (Roc), a C-terminal of Roc domain (COR), and a kinase domain. ...Several of the pathogenic mutations in LRRK2 res …
Human leucine rich repeat kinase 2 (LRRK2) belongs to the Roco family of proteins, which are characterized by the presence of a Ras-l …
Revisiting the Roco G-protein cycle.
Terheyden S, Ho FY, Gilsbach BK, Wittinghofer A, Kortholt A. Terheyden S, et al. Among authors: kortholt a. Biochem J. 2015 Jan 1;465(1):139-47. doi: 10.1042/BJ20141095. Biochem J. 2015. PMID: 25317655
LRRK2 belongs to the Roco family of proteins which share a conserved Ras-like G-domain (Roc) and a C-terminal of Roc (COR) domain tandem. ...Nucleotide binding induces a drastic structural change in the Roc/COR domain interface, a region strongly impli …
LRRK2 belongs to the Roco family of proteins which share a conserved Ras-like G-domain (Roc) and a C-terminal of Roc (COR) dom …
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