Bumping Up Kinase Activity with an ATP-Derived Neo-Substrate Ralph E. Kleiner, Tarun M. Kapoor  Cell  Volume 154, Issue 4, Pages 716-718 (August 2013) DOI: 10.1016/j.cell.2013.07.043 Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 1 Approaches to Modulate Cellular ATPase Activity in a Therapeutically Relevant Manner (A) Efforts to block receptor tyrosine kinase activation have led to the development of small-molecule inhibitors of the EGFR tyrosine kinase, which are FDA approved for the treatment of cancer. (B) In this issue, Shokat and colleagues (Hertz et al., 2013) describe an approach for increasing PINK1 kinase activity with an ATP-derived neo-substrate, KTP, which can be generated intracellularly by feeding cells kinetin. Impairment of PINK1 kinase activity leads to defects in the mitochondrial elimination pathway and has been linked to early-onset familial PD. (C) The neo-substrate strategy for ATPase activation presents a unique opportunity to increase the activity of other ATPases whose loss of function has been linked to human disease, such as members of the AAA+ family. Cell 2013 154, 716-718DOI: (10.1016/j.cell.2013.07.043) Copyright © 2013 Elsevier Inc. Terms and Conditions