NDLI: Death-Associated Protein Kinase Activity Is Regulated by Coupled Calcium/Calmodulin Binding to Two Distinct Sites

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Death-Associated Protein Kinase Activity Is Regulated by Coupled Calcium/Calmodulin Binding to Two Distinct Sites

Content Provider	PubMed Central
Author	Simon, Bertrand Huart, Anne-sophie Temmerman, Koen Juha, Vahokoski Mertens, HaydynÂ d. T. Komadina, Dana Hoffmann, Jan-erik Yumerefendi, Hayretin Svergun, DmitriÂ i. Petri, Kursula Schultz, Carsten Mccarthy, AndrewÂ a. Hart, DarrenÂ j. Wilmanns, Matthias
Copyright Year	2016
Abstract	The regulation of many protein kinases by binding to calcium/calmodulin connects two principal mechanisms in signaling processes: protein phosphorylation and responses to dose- and time-dependent calcium signals. We used the calcium/calmodulin-dependent members of the death-associated protein kinase (DAPK) family to investigate the role of a basic DAPK signature loop near the kinase active site. In DAPK2, this loop comprises a novel dimerization-regulated calcium/calmodulin-binding site, in addition to a well-established calcium/calmodulin site in the C-terminal autoregulatory domain. Unexpectedly, impairment of the basic loop interaction site completely abolishes calcium/calmodulin binding and DAPK2 activity is reduced to a residual level, indicative of coupled binding to the two sites. This contrasts with the generally accepted view that kinase calcium/calmodulin interactions are autonomous of the kinase catalytic domain. Our data establish an intricate model of multi-step kinase activation and expand our understanding of how calcium binding connects with other mechanisms involved in kinase activity regulation.
Related Links	http://dx.doi.org/10.1016/j.str.2016.03.020
Ending Page	861
Page Count	11
Starting Page	851
File Format	PDF
ISSN	18784186
e-ISSN	18784186
Journal	Structure(London, England:1993)
Issue Number	6
Volume Number	24
Language	English
Publisher	Cell Press
Publisher Date	2016-06-07
Access Restriction	Open
Rights Holder	Cell Press
Subject Keyword	macromolecular complexes structural genomics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Structural Biology Molecular Biology

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Death-Associated Protein Kinase Activity Is Regulated by Coupled Calcium/Calmodulin Binding to Two Distinct Sites.

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Death-Associated Protein Kinase Activity Is Regulated by Coupled Calcium/Calmodulin Binding to Two Distinct Sites

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Death-Associated Protein Kinase Activity Is Regulated by Coupled Calcium/Calmodulin Binding to Two Distinct Sites.

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Death-Associated Protein Kinase Activity Is Regulated by Coupled Calcium/Calmodulin Binding to Two Distinct Sites