Research Questions
MJFF will be closed next week, but we'll be back on September 7, 2010!
Below are the Papers of the Week. To comment on an individual paper, click on the manuscript title, then click "reply".
In a recent paper by Titz, et a. (2010), the authors investigated the organization of the BCR-ABL1 tyrosine kinase signaling complex using proteomic techniques and found LRRK1 (Leucine-Rich Repeat Kinase 1) to be a component. LRRK1 was found to differentially associate with one of three leukemia transformation-relevant adaptor protein complexes (Grb2/Gab2/Shc1, suggesting that it may participate in the mitogen-activated protein kinase response to cellular stress. Could this study highlight a novel activity for LRRK1? And how might this affect our understanding of LRRK2 function?
Below are the Papers of the Week. To comment on an individual paper, click on the manuscript title, then click "reply".
Below are the Papers of the Week. To comment on an individual paper, click on the manuscript title, then click "reply".
Do the correct research models already exist for the study of LRRK2? If not, what models should be generated? We're compiling a database of PD research models--please submit your model!
Is there a missing link between LRRK2 and synuclein? Is there a connection? If so, what could it be?
MJFF has successfully generated LRRK2 antibodies, a critical tool for PD scientists. These antibodies will allow LRRK2 researchers to answer several questions about LRRK2 such as, "What are its basic biochemical properties?" and "What is the cellular and subcellular localization of the normal protein?"
Of course the million dollar question is "What is going wrong with LRRK2 that ultimately results in the development of Parkinson's disease?" Often, protein kinases "go wrong" by aberrantly phosphorylating other proteins, a function that may well be in LRRK2's repertoire. But what if LRRK2 is itself aberrantly phosphorylated? How would that affect its function or localization? When does this happen? Which phosphorylated sites (if any) are physiologically relevant?
In an effort to take our understanding of LRRK2 function to the next level, MJFF is currently designing new phospho-specific LRRK2 antibodies that may help answer some of these nagging questions. While there are a number of potential sites, we have narrowed down the number of sites based on those that have been verified across several labs. The figure below delineates those 8 residues (indicated in red) within the context of the whole protein. Generation of polyclonal rabbit antibodies will begin shortly and those that are found to be specific will ultimately be made available to the entire research community.
Click on figure to enlarge
We'll update you on our progress -- so, check this space often!