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GTP binding and intramolecular regulation by the ROC domain of Death Associated Protein Kinase 1

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Jebelli, J. D., Dihanich, S., Civiero, L., Manzoni, C., Greggio, E. and Lewis, P. A. (2012) GTP binding and intramolecular regulation by the ROC domain of Death Associated Protein Kinase 1. Scientific Reports, 2. 695. ISSN 2045-2322

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To link to this article DOI: 10.1038/srep00695

Abstract/Summary

The ROCO proteins are a family of large, multidomain proteins characterised by the presence of a Ras of complex proteins (ROC) domain followed by a COR, or C-terminal of ROC, domain. It has previously been shown that the ROC domain of the human ROCO protein Leucine Rich Repeat Kinase 2 (LRRK2) controls its kinase activity. Here, the ability of the ROC domain of another human ROCO protein, Death Associated Protein Kinase 1 (DAPK1), to bind GTP and control its kinase activity has been evaluated. In contrast to LRRK2, loss of GTP binding by DAPK1 does not result in loss of kinase activity, instead acting to modulate this activity. These data highlight the ROC domain of DAPK1 as a target for modifiers of this proteins function, and casts light on the role of ROC domains as intramolecular regulators in complex proteins with implications for a broad range of human diseases.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
ID Code:29431
Publisher:Nature Publishing Group
Publisher Statement:This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. http://creativecommons.org/licenses/by-nc-nd/3.0/

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