PYK2 senses calcium through a disordered dimerization and calmodulin-binding element.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
09 08 2022
09 08 2022
Historique:
received:
14
12
2021
accepted:
22
07
2022
entrez:
9
8
2022
pubmed:
10
8
2022
medline:
12
8
2022
Statut:
epublish
Résumé
Multidomain kinases use many ways to integrate and process diverse stimuli. Here, we investigated the mechanism by which the protein tyrosine kinase 2-beta (PYK2) functions as a sensor and effector of cellular calcium influx. We show that the linker between the PYK2 kinase and FAT domains (KFL) encompasses an unusual calmodulin (CaM) binding element. PYK2 KFL is disordered and engages CaM through an ensemble of transient binding events. Calcium increases the association by promoting structural changes in CaM that expose auxiliary interaction opportunities. KFL also forms fuzzy dimers, and dimerization is enhanced by CaM binding. As a monomer, however, KFL associates with the PYK2 FERM-kinase fragment. Thus, we identify a mechanism whereby calcium influx can promote PYK2 self-association, and hence kinase-activating trans-autophosphorylation. Collectively, our findings describe a flexible protein module that expands the paradigms for CaM binding and self-association, and their use for controlling kinase activity.
Identifiants
pubmed: 35945264
doi: 10.1038/s42003-022-03760-8
pii: 10.1038/s42003-022-03760-8
pmc: PMC9363500
doi:
Substances chimiques
Calmodulin
0
Focal Adhesion Kinase 2
EC 2.7.10.2
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
800Informations de copyright
© 2022. The Author(s).
Références
Science. 1991 May 24;252(5009):1162-4
pubmed: 2031185
Biochemistry. 2019 Sep 10;58(36):3767-3776
pubmed: 31403288
Proc Natl Acad Sci U S A. 2014 Aug 5;111(31):E3177-86
pubmed: 25049397
Eur J Neurosci. 1999 Nov;11(11):3777-88
pubmed: 10583467
Mol Med. 1998 Dec;4(12):751-69
pubmed: 9990861
J Biol Chem. 1995 Sep 8;270(36):21206-19
pubmed: 7673154
Methods Enzymol. 2019;621:131-152
pubmed: 31128775
Bioinformatics. 2015 Apr 15;31(8):1325-7
pubmed: 25505092
Curr Opin Struct Biol. 2017 Feb;42:15-23
pubmed: 27794210
Nucleic Acids Res. 2019 Mar 18;47(5):2666-2680
pubmed: 30597093
Proteins. 2009 Jan;74(1):104-21
pubmed: 18615714
Front Synaptic Neurosci. 2021 Oct 06;13:749001
pubmed: 34690733
J Biol Chem. 2017 Mar 17;292(11):4614-4622
pubmed: 28174300
Neoplasia. 2005 May;7(5):435-45
pubmed: 15967096
J Cell Sci. 2007 Sep 1;120(Pt 17):3034-44
pubmed: 17684059
Bioinformatics. 2000 Apr;16(4):404-5
pubmed: 10869041
Bioinformatics. 2015 Mar 1;31(5):767-9
pubmed: 25338722
J Biol Chem. 1997 Apr 18;272(16):10941-7
pubmed: 9099753
Mol Brain. 2010 Jan 21;3:4
pubmed: 20180987
J Biol Chem. 2006 Jan 6;281(1):252-9
pubmed: 16221668
Sci Rep. 2019 Dec 31;9(1):20396
pubmed: 31892719
Bioinformatics. 2013 Jul 15;29(14):1750-7
pubmed: 23681122
Bioinformatics. 1998;14(10):892-3
pubmed: 9927721
Mol Endocrinol. 2008 Oct;22(10):2322-35
pubmed: 18635666
PLoS Comput Biol. 2018 Apr 3;14(4):e1006072
pubmed: 29614072
BMC Genomics. 2006 Aug 04;7:198
pubmed: 16889663
Cancers (Basel). 2018 Jun 11;10(6):
pubmed: 29891810
Prog Nucl Magn Reson Spectrosc. 2013 Aug;73:1-16
pubmed: 23962882
Sci Rep. 2013;3:1392
pubmed: 23462742
J Biol Chem. 2005 Apr 29;280(17):17397-407
pubmed: 15735309
Curr Opin Struct Biol. 2011 Dec;21(6):808-13
pubmed: 22030387
Biochemistry. 2002 Aug 20;41(33):10510-8
pubmed: 12173938
Biochim Biophys Acta. 2014 Jun;1844(6):1153-66
pubmed: 24704038
Solid State Nucl Magn Reson. 2014 May-Jun;59-60:31-3
pubmed: 24656572
Cell Mol Life Sci. 2013 Jan;70(1):137-52
pubmed: 22802128
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
Int Rev Cell Mol Biol. 2011;288:185-225
pubmed: 21482413
Biochem J. 2008 Mar 15;410(3):e3-4
pubmed: 18290763
J Cell Sci. 2010 Apr 1;123(Pt 7):1007-13
pubmed: 20332118
J Biol Chem. 2004 Aug 6;279(32):33315-22
pubmed: 15166227
Nature. 1995 Aug 31;376(6543):737-45
pubmed: 7544443
Trends Neurosci. 1999 Jun;22(6):257-63
pubmed: 10354603
J Biol Chem. 1996 Nov 22;271(47):29993-8
pubmed: 8939945
Nat Commun. 2016 Nov 23;7:13583
pubmed: 27876793
J Struct Biol. 2019 Jun 1;206(3):305-313
pubmed: 30951824
Proteins. 2005 Jun 1;59(4):662-72
pubmed: 15822098
Cell. 2007 Jun 15;129(6):1177-87
pubmed: 17574028
Biochemistry. 2012 Sep 25;51(38):7456-64
pubmed: 22947085
Methods Mol Biol. 2004;278:353-78
pubmed: 15318003
J Biol Chem. 1996 Nov 15;271(46):28942-6
pubmed: 8910543
Prog Biophys Mol Biol. 2015 Oct;119(1):60-71
pubmed: 26093249
Structure. 2002 Mar;10(3):319-27
pubmed: 12005431
Elife. 2021 Mar 03;10:
pubmed: 33655882
J Biomol NMR. 2013 Jul;56(3):227-41
pubmed: 23728592
Cell Signal. 2000 Mar;12(3):123-33
pubmed: 10704819
Curr Protoc Protein Sci. 2013 Feb;Chapter 20:Unit20.12
pubmed: 23377850
Biochemistry. 2004 Feb 24;43(7):2049-61
pubmed: 14967045
J Neurosci. 2010 Jan 13;30(2):449-63
pubmed: 20071509
Mol Cell. 2008 Jan 18;29(1):9-22
pubmed: 18206965
Nat Struct Biol. 2002 Feb;9(2):101-6
pubmed: 11799401
J Neurochem. 1994 Mar;62(3):950-9
pubmed: 7509378
Int J Mol Sci. 2020 Nov 16;21(22):
pubmed: 33207556
Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5192-6
pubmed: 1594631
J Biol Chem. 2001 May 18;276(20):17199-205
pubmed: 11278857
Nat Rev Cancer. 2014 Sep;14(9):598-610
pubmed: 25098269
EMBO Rep. 2006 Nov;7(11):1117-23
pubmed: 17039254
Mol Cell Biol. 1999 Mar;19(3):2338-50
pubmed: 10022920
J Biol Chem. 2011 Nov 25;286(47):40954-61
pubmed: 21931166
EMBO J. 2014 Feb 18;33(4):356-70
pubmed: 24480479
Methods Enzymol. 1996;266:525-39
pubmed: 8743704
Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8487-91
pubmed: 1528852
J Cell Biol. 1997 Oct 20;139(2):529-39
pubmed: 9334354
Biochem J. 2008 Mar 15;410(3):513-23
pubmed: 18031286
Mol Cell Biol. 2002 Nov;22(22):7731-43
pubmed: 12391143
PLoS One. 2015 Jun 26;10(6):e0130478
pubmed: 26114780
J Biol Chem. 1997 Aug 1;272(31):19125-32
pubmed: 9235901
Neuron. 2001 Feb;29(2):485-96
pubmed: 11239437
Anal Biochem. 2004 Mar 15;326(2):234-56
pubmed: 15003564
Nat Rev Cancer. 2005 Jul;5(7):505-15
pubmed: 16069815
Structure. 2012 Mar 7;20(3):522-33
pubmed: 22405011
J Gen Physiol. 2014 Jul;144(1):105-14
pubmed: 24935744
Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17797-802
pubmed: 22006323
Nat Struct Biol. 2003 Mar;10(3):226-31
pubmed: 12577052
Biochemistry. 2008 Dec 16;47(50):13428-37
pubmed: 19086274