GTP binding to the ROC domain of DAP-kinase regulates its function through intramolecular signalling

被引：34

作者：

Carlessi, Rodrigo ^{[1
]}

Levin-Salomon, Vered ^{[1
]}

Ciprut, Sara ^{[1
]}

Bialik, Shani ^{[1
]}

Berissi, Hanna ^{[1
]}

Albeck, Shira ^{[2
]}

Peleg, Yoav ^{[2
]}

Kimchi, Adi ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel

[2] Weizmann Inst Sci, Israel Struct Prote Ctr, IL-76100 Rehovot, Israel

来源：

EMBO REPORTS | 2011年 / 12卷 / 09期

关键词：

GTP-binding proteins; DAP-kinase; ROCO family; LRRK2; PROTEIN-KINASE; CELL-DEATH; PARKINSONS-DISEASE; LEUCINE-RICH-REPEAT-KINASE-2; LRRK2; AUTOPHOSPHORYLATION; COMPLEX;

D O I：

10.1038/embor.2011.126

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Death-associated protein kinase (DAPk) was recently suggested by sequence homology to be a member of the ROCO family of proteins. Here, we show that DAPk has a functional ROC (Ras of complex proteins) domain that mediates homo-oligomerization and GTP binding through a defined P-loop motif. Upon binding to GTP, the ROC domain negatively regulates the catalytic activity of DAPk and its cellular effects. Mechanistically, GTP binding enhances an inhibitory autophosphorylation at a distal site that suppresses kinase activity. This study presents a new mechanism of intramolecular signal transduction, by which GTP binding operates in cis to affect the catalytic activity of a distal domain in the protein.

引用

页码：917 / 923

页数：7

共 19 条

[1] DAP-kinase as a target for drug design in cancer and diseases associated with accelerated cell death
Bialik, S
Kimchi, A
[J]. SEMINARS IN CANCER BIOLOGY, 2004, 14 (04) : 283 - 294
[2] The death-associated protein kinases: Structure, function, and beyond
Bialik, Shani
Kimchi, Adi
[J]. ANNUAL REVIEW OF BIOCHEMISTRY, 2006, 75 : 189 - 210
[3] Roc, a Ras/GTPase domain in complex proteins
Bosgraaf, L
Van Haastert, PJM
[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2003, 1643 (1-3): : 5 - 10
[4] DAP-kinase is a Ca2+ calmodulin-dependent, cytoskeletal-associated protein kinase, with cell death-inducing functions that depend on its catalytic activity
Cohen, O
Feinstein, E
Kimchi, A
[J]. EMBO JOURNAL, 1997, 16 (05) : 998 - 1008
[5] Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant
Daniels, Veronique
Vancraenenbroeck, Renee
Law, Bernard M. H.
Greggio, Elisa
Lobbestael, Evy
Gao, Fangye
De Maeyer, Marc
Cookson, Mark R.
Harvey, Kirsten
Baekelandt, Veerle
Taymans, Jean-Marc
[J]. JOURNAL OF NEUROCHEMISTRY, 2011, 116 (02) : 304 - 315
[6] Molecular Basis of the Death-Associated Protein Kinase-Calcium/Calmodulin Regulator Complex
de Diego, Inaki
Kuper, Jochen
Bakalova, Neda
Kursula, Petri
Wilmanns, Matthias
[J]. SCIENCE SIGNALING, 2010, 3 (106) : ra6
[7] Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase
Deng, Junpeng
Lewis, Patrick A.
Greggio, Elisa
Sluch, Eli
Beilina, Alexandra
Cookson, Mark R.
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (05) : 1499 - 1504
[8] Structure of the Roc-COR domain tandem of C-tepidum, a prokaryotic homologue of the human LRRK2 Parkinson kinase
Gotthardt, Katja
Weyand, Michael
Kortholt, Arjan
Van Haastert, Peter J. M.
Wittinghofer, Alfred
[J]. EMBO JOURNAL, 2008, 27 (16) : 2239 - 2249
[9] DAP-kinase is a mediator of endoplasmic reticulum stress-induced caspase activation and autophagic cell death
Gozuacik, D.
Bialik, S.
Raveh, T.
Mitou, G.
Shohat, G.
Sabanay, H.
Mizushima, N.
Yoshimori, T.
Kimchi, A.
[J]. CELL DEATH AND DIFFERENTIATION, 2008, 15 (12) : 1875 - 1886
[10] The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation
Greggio, Elisa
Zambrano, Ibardo
Kaganovich, Alice
Beilina, Alexandra
Taymans, Jean-Marc
Daniels, Veronique
Lewis, Patrick
Jain, Shushant
Ding, Jinhui
Syed, Ali
Thomas, Kelly J.
Baekelandt, Veerle
Cookson, Mark R.
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (24) : 16906 - 16914

← 1 2 →