The Parkinson’s disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites
Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of inherited Parkinson’s disease (PD). The protein is large and complex, but pathogenic mutations cluster in a region containing GTPase and kinase domains. LRRK2 can autophosphorylate in vitro within a dimer pair, although the sign...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2009-11, Vol.389 (3), p.449-454 |
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| creator | Greggio, Elisa Taymans, Jean-Marc Zhen, Eugene Yuejun Ryder, John Vancraenenbroeck, Renée Beilina, Alexandra Sun, Peng Deng, Junpeng Jaffe, Howard Baekelandt, Veerle Merchant, Kalpana Cookson, Mark R. |
| description | Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of inherited Parkinson’s disease (PD). The protein is large and complex, but pathogenic mutations cluster in a region containing GTPase and kinase domains. LRRK2 can autophosphorylate
in vitro within a dimer pair, although the significance of this reaction is unclear. Here, we mapped the sites of autophosphorylation within LRRK2 and found several potential phosphorylation sites within the GTPase domain. Using mass spectrometry, we found that Thr1343 is phosphorylated and, using kinase dead versions of LRRK2, show that this is an autophosphorylation site. However, we also find evidence for additional sites in the GTPase domain and in other regions of the protein suggesting that there may be multiple autophosphorylation sites within LRRK2. These data suggest that the kinase and GTPase activities of LRRK2 may exhibit complex autoregulatory interdependence. |
| doi_str_mv | 10.1016/j.bbrc.2009.08.163 |
| format | Article |
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These data suggest that the kinase and GTPase activities of LRRK2 may exhibit complex autoregulatory interdependence.</description><subject>Amino Acid Sequence</subject><subject>Autophosphorylation</subject><subject>Cell Line</subject><subject>GTP Phosphohydrolases - genetics</subject><subject>GTP Phosphohydrolases - metabolism</subject><subject>GTPase</subject><subject>Humans</subject><subject>Kinase</subject><subject>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Parkinson Disease - enzymology</subject><subject>Parkinson Disease - genetics</subject><subject>Parkinson’s disease</subject><subject>Phosphorylation</subject><subject>Protein Structure, Tertiary - genetics</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Threonine - genetics</subject><subject>Threonine - metabolism</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAQxy1ERZfCC3BAPnFLGH_EcSSEhKpSECtRVXvggizHmbBeknixk0q98Rq8Xp-ERLvi49IerJE8v_nLnh8hLxjkDJh6vcvrOrqcA1Q56Jwp8YisGFSQcQbyMVkBgMp4xb6ckqcp7QAYk6p6Qk5ZVQrBCr4iXzdbpFc2fvdDCsPdz1-JNj6hTUjnq6Wsr68_cWqnMey3Ic0n3nZ2xET9mOjl5mphmtBbP1A70n7qRr_vkCY_M8_ISWu7hM-P9Yxs3l9szj9k68-XH8_frTMntRyzGtpWNZILaQtZlaVVwF1d2lKAbrRTohYVR6VlK5iqlRBatFpoVLYpsJHijLw9xO6nusfG4TBG25l99L2NtyZYb_7vDH5rvoUbw8ui0lLNAa-OATH8mDCNpvfJYdfZAcOUjCqVLrhkD4IcKsW54DPID6CLIaWI7Z_XMDCLPbMziz2z2DOgzWxvHnr57z_-jhx1zcCbA4DzMm88RpOcx8Fh4yO60TTB35f_G8JNrb0</recordid><startdate>20091120</startdate><enddate>20091120</enddate><creator>Greggio, Elisa</creator><creator>Taymans, Jean-Marc</creator><creator>Zhen, Eugene Yuejun</creator><creator>Ryder, John</creator><creator>Vancraenenbroeck, Renée</creator><creator>Beilina, Alexandra</creator><creator>Sun, Peng</creator><creator>Deng, Junpeng</creator><creator>Jaffe, Howard</creator><creator>Baekelandt, Veerle</creator><creator>Merchant, Kalpana</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20091120</creationdate><title>The Parkinson’s disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites</title><author>Greggio, Elisa ; 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| ispartof | Biochemical and biophysical research communications, 2009-11, Vol.389 (3), p.449-454 |
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| subjects | Amino Acid Sequence Autophosphorylation Cell Line GTP Phosphohydrolases - genetics GTP Phosphohydrolases - metabolism GTPase Humans Kinase Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Molecular Sequence Data Mutation Parkinson Disease - enzymology Parkinson Disease - genetics Parkinson’s disease Phosphorylation Protein Structure, Tertiary - genetics Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Threonine - genetics Threonine - metabolism |
| title | The Parkinson’s disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites |
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