کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1933526 1050616 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The Parkinson’s disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
The Parkinson’s disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 389, Issue 3, 20 November 2009, Pages 449–454
نویسندگان
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