Journal
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume 38, Issue 9, Pages 1469-1475Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2006.02.009
Keywords
leucine-rich repeat kinase 2; GTPase; signal transduction; Parkinson's disease
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Human leucine-rich repeat kinase 2 (LRRK2) is a novel kinase belonging to the ROCO protein superfamily (Ras of complex proteins (Roc) with a C-terminal of Roc domain). This large complex protein of 280 kDa contains several functional domains including leucine-rich repeats, Ras-related GTPase, mitogen-activated protein kinase kinase kinase (MAPKKK). and WD40 repeats. While definitive functions of LRRK2 have yet to be described. the domain structure of LRRK2 suggests that it plays an important role in the regulation of signal transduction cascades through its dual enzymatic activities of GTPase and MAPKKK. Moreover, mutations in LRRK2 have been found to be thus far the most frequent cause of late-onset familial and idiopathic Parkinson's disease. Further investigations should allow for the elucidation of how pathogenic mutations trigger changes in the structure and function of LRRK2 that lead to aberrant signal transduction and neurodegeneration in Parkinson's disease. (c) 2006 Elsevier Ltd. All rights reserved.
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