The R1441C mutation of LRRK2 disrupts GTP hydrolysis
Mutations in Leucine Rich Repeat Kinase 2 (LRRK2) are the leading genetic cause of Parkinson’s disease (PD). LRRK2 is predicted to contain kinase and GTPase enzymatic domains, with recent evidence suggesting that the kinase activity of LRRK2 is central to the pathogenic process associated with this...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2007-06, Vol.357 (3), p.668-671 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Lewis, Patrick A. Greggio, Elisa Beilina, Alexandra Jain, Shushant Baker, Acacia Cookson, Mark R. |
| description | Mutations in Leucine Rich Repeat Kinase 2 (LRRK2) are the leading genetic cause of Parkinson’s disease (PD). LRRK2 is predicted to contain kinase and GTPase enzymatic domains, with recent evidence suggesting that the kinase activity of LRRK2 is central to the pathogenic process associated with this protein. The GTPase domain of LRRK2 plays an important role in the regulation of kinase activity. To investigate how the GTPase domain might be related to disease, we examined the GTP binding and hydrolysis properties of wild type and a mutant form of LRRK2. We show that LRRK2 immunoprecipitated from cells has a detectable GTPase activity that is disrupted by a familial mutation associated with PD located within the GTPase domain, R1441C. |
| doi_str_mv | 10.1016/j.bbrc.2007.04.006 |
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LRRK2 is predicted to contain kinase and GTPase enzymatic domains, with recent evidence suggesting that the kinase activity of LRRK2 is central to the pathogenic process associated with this protein. The GTPase domain of LRRK2 plays an important role in the regulation of kinase activity. To investigate how the GTPase domain might be related to disease, we examined the GTP binding and hydrolysis properties of wild type and a mutant form of LRRK2. 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LRRK2 is predicted to contain kinase and GTPase enzymatic domains, with recent evidence suggesting that the kinase activity of LRRK2 is central to the pathogenic process associated with this protein. The GTPase domain of LRRK2 plays an important role in the regulation of kinase activity. To investigate how the GTPase domain might be related to disease, we examined the GTP binding and hydrolysis properties of wild type and a mutant form of LRRK2. We show that LRRK2 immunoprecipitated from cells has a detectable GTPase activity that is disrupted by a familial mutation associated with PD located within the GTPase domain, R1441C.</description><subject>Amino Acid Substitution</subject><subject>Animals</subject><subject>Cercopithecus aethiops</subject><subject>COS Cells</subject><subject>Dardarin</subject><subject>GTP Phosphohydrolases - genetics</subject><subject>GTP Phosphohydrolases - metabolism</subject><subject>GTPase</subject><subject>Guanosine Diphosphate - metabolism</subject><subject>Guanosine Triphosphate - metabolism</subject><subject>Humans</subject><subject>Hydrolysis</subject><subject>Immunoblotting</subject><subject>Immunoprecipitation</subject><subject>Kinase</subject><subject>Kinetics</subject><subject>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</subject><subject>LRRK2</subject><subject>Mutation</subject><subject>Parkinson Disease - enzymology</subject><subject>Parkinson Disease - genetics</subject><subject>Parkinson’s disease</subject><subject>Protein Binding</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1r4zAQhkXpsk3b_QM9FJ96s3dGliUbSqGENrtsYEvIwt6EI48bBcdKJTuQf1-HhH5cdnUZkJ55Gc3D2BVCgoDy-ypZLLxJOIBKQCQA8oSNEAqIOYI4ZSMYrmJe4N8zdh7CCgBRyOIrO0MlBOdSjZiYLymaoRA4jtZ9V3bWtZGro-ls9otHlQ2-33QhmsyfouWu8q7ZBRsu2Ze6bAJ9O9YL9ufxYT7-EU9_T36O76exyTLoYi4kKZ4VlPGKSOVUi1wKA2i4ynMCFArrqhayJG441rzmi8yQzEAqg2mWXrC7Q-6mX6ypMtR2vmz0xtt16XfalVZ_fmntUj-7rcYiLQqVDgE3xwDvXnoKnV7bYKhpypZcH7QCMZyc_xfEQspcZmIA-QE03oXgqX6bBkHvreiV3lvReysahB4UDE3XH__x3nLUMAC3B4CGbW4teR2MpdZQZT2ZTlfO_iv_FVXJnDk</recordid><startdate>20070608</startdate><enddate>20070608</enddate><creator>Lewis, Patrick A.</creator><creator>Greggio, Elisa</creator><creator>Beilina, Alexandra</creator><creator>Jain, Shushant</creator><creator>Baker, Acacia</creator><creator>Cookson, Mark R.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20070608</creationdate><title>The R1441C mutation of LRRK2 disrupts GTP hydrolysis</title><author>Lewis, Patrick A. ; Greggio, Elisa ; Beilina, Alexandra ; Jain, Shushant ; Baker, Acacia ; Cookson, Mark R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c550t-246e7259e52dee78ef4864c01c2788e01471fdf46ae2c21f2f2b5ce65067c1353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Amino Acid Substitution</topic><topic>Animals</topic><topic>Cercopithecus aethiops</topic><topic>COS Cells</topic><topic>Dardarin</topic><topic>GTP Phosphohydrolases - genetics</topic><topic>GTP Phosphohydrolases - metabolism</topic><topic>GTPase</topic><topic>Guanosine Diphosphate - metabolism</topic><topic>Guanosine Triphosphate - metabolism</topic><topic>Humans</topic><topic>Hydrolysis</topic><topic>Immunoblotting</topic><topic>Immunoprecipitation</topic><topic>Kinase</topic><topic>Kinetics</topic><topic>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</topic><topic>LRRK2</topic><topic>Mutation</topic><topic>Parkinson Disease - enzymology</topic><topic>Parkinson Disease - genetics</topic><topic>Parkinson’s disease</topic><topic>Protein Binding</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lewis, Patrick A.</creatorcontrib><creatorcontrib>Greggio, Elisa</creatorcontrib><creatorcontrib>Beilina, Alexandra</creatorcontrib><creatorcontrib>Jain, Shushant</creatorcontrib><creatorcontrib>Baker, Acacia</creatorcontrib><creatorcontrib>Cookson, Mark R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lewis, Patrick A.</au><au>Greggio, Elisa</au><au>Beilina, Alexandra</au><au>Jain, Shushant</au><au>Baker, Acacia</au><au>Cookson, Mark R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The R1441C mutation of LRRK2 disrupts GTP hydrolysis</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2007-06-08</date><risdate>2007</risdate><volume>357</volume><issue>3</issue><spage>668</spage><epage>671</epage><pages>668-671</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Mutations in Leucine Rich Repeat Kinase 2 (LRRK2) are the leading genetic cause of Parkinson’s disease (PD). LRRK2 is predicted to contain kinase and GTPase enzymatic domains, with recent evidence suggesting that the kinase activity of LRRK2 is central to the pathogenic process associated with this protein. The GTPase domain of LRRK2 plays an important role in the regulation of kinase activity. To investigate how the GTPase domain might be related to disease, we examined the GTP binding and hydrolysis properties of wild type and a mutant form of LRRK2. We show that LRRK2 immunoprecipitated from cells has a detectable GTPase activity that is disrupted by a familial mutation associated with PD located within the GTPase domain, R1441C.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>17442267</pmid><doi>10.1016/j.bbrc.2007.04.006</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Biochemical and biophysical research communications, 2007-06, Vol.357 (3), p.668-671 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Amino Acid Substitution Animals Cercopithecus aethiops COS Cells Dardarin GTP Phosphohydrolases - genetics GTP Phosphohydrolases - metabolism GTPase Guanosine Diphosphate - metabolism Guanosine Triphosphate - metabolism Humans Hydrolysis Immunoblotting Immunoprecipitation Kinase Kinetics Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 LRRK2 Mutation Parkinson Disease - enzymology Parkinson Disease - genetics Parkinson’s disease Protein Binding Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism |
| title | The R1441C mutation of LRRK2 disrupts GTP hydrolysis |
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