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Articles

How many kinases are druggable? A review of our current understanding

Brian Anderson, Peter Rosston, Han Wee Ong, Mohammad Anwar Hossain, Zachary W. Davis-Gilbert, David H. Drewry

Biochem J (2023) 480 (16): 1331–1363.

https://doi.org/10.1042/BCJ20220217

Published: 29 August 2023

...Brian Anderson; Peter Rosston; Han Wee Ong; Mohammad Anwar Hossain; Zachary W. Davis-Gilbert; David H. Drewry There are over 500 human kinases ranging from very well-studied to almost completely ignored. Kinases are tractable and implicated in many diseases, making them ideal targets for medicinal...

View article titled, How many kinases are druggable? A review of our current understanding

Includes: Supplementary data

Articles

Evolutionary and cellular analysis of the ‘dark’ pseudokinase PSKH2

In Collection

Cell signaling in the 21st century

Dominic P. Byrne, Safal Shrestha, Leonard A. Daly, Vanessa Marensi, Krithika Ramakrishnan, Claire E. Eyers, Natarajan Kannan, Patrick A. Eyers

Biochem J (2023) 480 (2): 141–160.

https://doi.org/10.1042/BCJ20220474

Published: 23 January 2023

... a variety of biological functions in both prokaryotic and eukaryotic organisms. Human PSKH2 is closely related to the canonical kinase PSKH1, which maps to the CAMK family of protein kinases. Primates encode PSKH2 in the form of a pseudokinase, which is predicted to be catalytically inactive due to loss...

View article titled, Evolutionary and cellular analysis of the ‘dark’ pseudokinase PSKH2

Includes: Multimedia, Supplementary data

Articles

Orchestrating serine/threonine phosphorylation and elucidating downstream effects by short linear motifs

Johanna Kliche, Ylva Ivarsson

Biochem J (2022) 479 (1): 1–22.

https://doi.org/10.1042/BCJ20200714

Published: 06 January 2022

..., such as phosphorylation, that create and break motif binding sites or tune the affinity of the interactions. In addition, motif-based interactions are involved in targeting serine/threonine kinases and phosphatases to their substrate and contribute to the specificity of the enzymatic actions regulating which sites...

View article titled, Orchestrating serine/threonine phosphorylation and elucidating downstream effects by short linear motifs

Articles

Impact of Type II LRRK2 inhibitors on signaling and mitophagy

Anna Tasegian, Francois Singh, Ian G. Ganley, Alastair D. Reith, Dario R. Alessi

Biochem J (2021) 478 (19): 3555–3573.

https://doi.org/10.1042/BCJ20210375

Published: 06 October 2021

... and MLi-2) and Type II (GZD-824, Rebastinib and Ponatinib) kinase inhibitors that bind to the closed or open conformations of the LRRK2 kinase domain, respectively. We show that Type I and Type II inhibitors suppress phosphorylation of Rab10 and Rab12, key physiological substrates of LRRK2 and also...

View article titled, Impact of Type II LRRK2 inhibitors on signaling and mitophagy

Includes: Supplementary data

Articles

Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms

In Collection

Protein structure and function

Asad U. Malik, Athanasios Karapetsas, Raja S. Nirujogi, Sebastian Mathea, Deep Chatterjee, Prosenjit Pal, Pawel Lis, Matthew Taylor, Elena Purlyte, Robert Gourlay, Mark Dorward, Simone Weidlich, Rachel Toth, Nicole K. Polinski, Stefan Knapp, Francesca Tonelli, Dario R. Alessi

Biochem J (2021) 478 (3): 553–578.

https://doi.org/10.1042/BCJ20200937

Published: 10 February 2021

... mutations in LRRK2 that enhance kinase activity cause Parkinson's disease. LRRK2 phosphorylates a subset of Rab GTPases including Rab8A and Rab10 within its effector binding motif. Here, we explore whether LRRK1, a less studied homolog of LRRK2 that regulates growth factor receptor trafficking...

View article titled, Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms

Includes: Supplementary data

Articles

The structure of human GCN2 reveals a parallel, back-to-back kinase dimer with a plastic DFG activation loop motif

Taiana Maia de Oliveira, Victoria Korboukh, Sarah Caswell, Jon J. Winter Holt, Michelle Lamb, Alexander W. Hird, Ross Overman

Biochem J (2020) 477 (1): 275–284.

https://doi.org/10.1042/BCJ20190196

Published: 17 January 2020

...Taiana Maia de Oliveira; Victoria Korboukh; Sarah Caswell; Jon J. Winter Holt; Michelle Lamb; Alexander W. Hird; Ross Overman When activated by amino acid starvation, the stress sensing protein kinase GCN2 phosphorylates the eukaryotic initiation factor 2 alpha, inhibiting translation to conserve...

View article titled, The structure of human GCN2 reveals a parallel, back-to-back kinase dimer with a plastic DFG activation loop motif

Includes: Supplementary data

Articles

Lessons from LIMK1 enzymology and their impact on inhibitor design

Eidarus Salah, Deep Chatterjee, Alessandra Beltrami, Anthony Tumber, Franziska Preuss, Peter Canning, Apirat Chaikuad, Petra Knaus, Stefan Knapp, Alex N. Bullock, Sebastian Mathea

Biochem J (2019) 476 (21): 3197–3209.

https://doi.org/10.1042/BCJ20190517

Published: 05 November 2019

...Eidarus Salah; Deep Chatterjee; Alessandra Beltrami; Anthony Tumber; Franziska Preuss; Peter Canning; Apirat Chaikuad; Petra Knaus; Stefan Knapp; Alex N. Bullock; Sebastian Mathea LIM domain kinase 1 (LIMK1) is a key regulator of actin dynamics. It is thereby a potential therapeutic target...

View article titled, Lessons from LIMK1 enzymology and their impact on inhibitor design

Includes: Supplementary data

Articles

Solution structures and biophysical analysis of full-length group A PAKs reveal they are monomeric and auto-inhibited in cis

Fiona J. Sorrell, Lena Marie Kilian, Jonathan M. Elkins

Biochem J (2019) 476 (7): 1037–1051.

https://doi.org/10.1042/BCJ20180867

Published: 04 April 2019

...Fiona J. Sorrell; Lena Marie Kilian; Jonathan M. Elkins The group A p21-activated kinases (PAKs) exist in an auto-inhibited form until activated by GTPase binding and auto-phosphorylation. In the auto-inhibited form, a regulatory domain binds to the kinase domain (KD) blocking the binding...

View article titled, Solution structures and biophysical analysis of full-length group A PAKs reveal they are monomeric and auto-inhibited in cis

Includes: Supplementary data

Articles

Kinase activity of mutant LRRK2 manifests differently in hetero-dimeric vs. homo-dimeric complexes

In Collection

Editors' pick of research highlights published in the Biochemical Journal in 2018 & 2019

Emmanouela Leandrou, Eliana Markidi, Anna Memou, Katerina Melachroinou, Elisa Greggio, Hardy J. Rideout

Biochem J (2019) 476 (3): 559–579.

https://doi.org/10.1042/BCJ20180589

Published: 08 February 2019

...Emmanouela Leandrou; Eliana Markidi; Anna Memou; Katerina Melachroinou; Elisa Greggio; Hardy J. Rideout The Parkinson's disease (PD) protein leucine-rich repeat kinase 2 (LRRK2) exists as a mixture of monomeric and dimeric species, with its kinase activity highly concentrated in the dimeric...

View article titled, Kinase activity of mutant LRRK2 manifests differently in hetero-dimeric vs. homo-dimeric complexes

Includes: Supplementary data

Articles

New tools for carbohydrate sulfation analysis: heparan sulfate 2- O -sulfotransferase (HS2ST) is a target for small-molecule protein kinase inhibitors

Dominic P. Byrne, Yong Li, Krithika Ramakrishnan, Igor L. Barsukov, Edwin A. Yates, Claire E. Eyers, Dulcé Papy-Garcia, Sandrine Chantepie, Vijayakanth Pagadala, Jian Liu, Carrow Wells, David H. Drewry, William J. Zuercher, Neil G. Berry, David G. Fernig, Patrick A. Eyers

Biochem J (2018) 475 (15): 2417–2433.

https://doi.org/10.1042/BCJ20180265

Published: 14 August 2018

... sulfation using a novel synthetic fluorescent substrate and screen the Published Kinase Inhibitor Set, to evaluate compounds that inhibit catalysis. We report the susceptibility of HS2ST to a variety of cell-permeable compounds in vitro , including polyanionic polar molecules, the protein kinase inhibitor...

View article titled, New tools for carbohydrate sulfation analysis: heparan sulfate 2- O -sulfotransferase (HS2ST) is a target for small-molecule protein kinase inhibitors

Includes: Supplementary data

Articles

The Parkinson's disease VPS35[D620N] mutation enhances LRRK2-mediated Rab protein phosphorylation in mouse and human

In Collection

Editors' pick of research highlights published in the Biochemical Journal in 2018 & 2019

Rafeeq Mir, Francesca Tonelli, Pawel Lis, Thomas Macartney, Nicole K. Polinski, Terina N. Martinez, Meng-Yun Chou, Andrew J.M. Howden, Theresa König, Christoph Hotzy, Ivan Milenkovic, Thomas Brücke, Alexander Zimprich, Esther Sammler, Dario R. Alessi

Biochem J (2018) 475 (11): 1861–1883.

https://doi.org/10.1042/BCJ20180248

Published: 06 June 2018

... repeat protein kinase-2) and VPS35 genes result in autosomal dominant Parkinson's disease. The VPS35 gene encodes for the cargo-binding component of the retromer complex, while LRRK2 modulates vesicular trafficking by phosphorylating a subgroup of Rab proteins. Pathogenic mutations in LRRK2 increase its...

View article titled, The Parkinson's disease VPS35[D620N] mutation enhances LRRK2-mediated Rab protein phosphorylation in mouse and human

Includes: Supplementary data

Articles

Assaying kinase activity of the TPL-2/NF-κB1 p105/ABIN-2 complex using an optimal peptide substrate

Sandra Kümper, Thorsten Gantke, Chao-Sheng Chen, Yasmina Soneji, Michael J. Pattison, Probir Chakravarty, Svend Kjær, Daniel Thomas, Carl Haslam, Bill J. Leavens, David House, David J. Powell, Steven C. Ley

Biochem J (2018) 475 (1): 329–340.

https://doi.org/10.1042/BCJ20170579

Published: 11 January 2018

...Sandra Kümper; Thorsten Gantke; Chao-Sheng Chen; Yasmina Soneji; Michael J. Pattison; Probir Chakravarty; Svend Kjær; Daniel Thomas; Carl Haslam; Bill J. Leavens; David House; David J. Powell; Steven C. Ley The MKK1/2 kinase tumour progression locus 2 (TPL-2) is critical for the production...

View article titled, Assaying kinase activity of the TPL-2/NF-κB1 p105/ABIN-2 complex using an optimal peptide substrate

Includes: Supplementary data

Articles

Redox regulation of a guard cell SNF1-related protein kinase in Brassica napus , an oilseed crop

Mengmeng Zhu, Tong Zhang, Wei Ji, Cecilia Silva-Sanchez, Wen-yuan Song, Sarah M. Assmann, Alice C. Harmon, Sixue Chen

Biochem J (2017) 474 (15): 2585–2599.

https://doi.org/10.1042/BCJ20170070

Published: 18 July 2017

...Mengmeng Zhu; Tong Zhang; Wei Ji; Cecilia Silva-Sanchez; Wen-yuan Song; Sarah M. Assmann; Alice C. Harmon; Sixue Chen Kinase-mediated phosphorylation is a pivotal regulatory process in stomatal responses to stresses. Through a redox proteomics study, a sucrose non-fermenting 1-related protein...

View article titled, Redox regulation of a guard cell SNF1-related protein kinase in Brassica napus , an oilseed crop

Includes: Supplementary data

Articles

Ubiquitin and Parkinson's disease through the looking glass of genetics

Helen Walden, Miratul M.K. Muqit

Biochem J (2017) 474 (9): 1439–1451.

https://doi.org/10.1042/BCJ20160498

Published: 13 April 2017

... in the ubiquitin system was linked to PD remained mysterious. The discovery of mutations in the α-synuclein gene, which encodes the main protein misfolded in PD aggregates, together with mutations in genes encoding ubiquitin regulatory molecules, including PTEN-induced kinase 1 (PINK1), Parkin, and FBX07, has...

View article titled, Ubiquitin and Parkinson's disease through the looking glass of genetics

Articles

Structure and inhibitor specificity of the PCTAIRE-family kinase CDK16

Sarah E. Dixon-Clarke, Saifeldin N. Shehata, Tobias Krojer, Timothy D. Sharpe, Frank von Delft, Kei Sakamoto, Alex N. Bullock

Biochem J (2017) 474 (5): 699–713.

https://doi.org/10.1042/BCJ20160941

Published: 20 February 2017

...Sarah E. Dixon-Clarke; Saifeldin N. Shehata; Tobias Krojer; Timothy D. Sharpe; Frank von Delft; Kei Sakamoto; Alex N. Bullock CDK16 (also known as PCTAIRE1 or PCTK1) is an atypical member of the cyclin-dependent kinase (CDK) family that has emerged as a key regulator of neurite outgrowth, vesicle...

View article titled, Structure and inhibitor specificity of the PCTAIRE-family kinase CDK16

Includes: Supplementary data

Articles

From the research laboratory to the database: the Caenorhabditis elegans kinome in UniProtKB

Rossana Zaru, Michele Magrane, Claire O'Donovan, the UniProt Consortium

Biochem J (2017) 474 (4): 493–515.

https://doi.org/10.1042/BCJ20160991

Published: 03 February 2017

...Rossana Zaru; Michele Magrane; Claire O'Donovan; the UniProt Consortium Protein kinases form one of the largest protein families and are found in all species, from viruses to humans. They catalyze the reversible phosphorylation of proteins, often modifying their activity and localization...

View article titled, From the research laboratory to the database: the Caenorhabditis elegans kinome in UniProtKB

Includes: Supplementary data

Articles

Molecular determinants of KA1 domain-mediated autoinhibition and phospholipid activation of MARK1 kinase

Ryan P. Emptage, Mark A. Lemmon, Kathryn M. Ferguson

Biochem J (2017) 474 (3): 385–398.

https://doi.org/10.1042/BCJ20160792

Published: 20 January 2017

...Ryan P. Emptage; Mark A. Lemmon; Kathryn M. Ferguson Protein kinases are frequently regulated by intramolecular autoinhibitory interactions between protein modules that are reversed when these modules bind other ‘activating’ protein or membrane-bound targets. One group of kinases, the M AP/ m...

View article titled, Molecular determinants of KA1 domain-mediated autoinhibition and phospholipid activation of MARK1 kinase

Includes: Supplementary data

Articles

Uncoupling JAK2 V617F activation from cytokine-induced signalling by modulation of JH2 αC helix

Emilie Leroy, Alexandra Dusa, Didier Colau, Amir Motamedi, Xavier Cahu, Céline Mouton, Lily J. Huang, Andrew K. Shiau, Stefan N. Constantinescu

Biochem J (2016) 473 (11): 1579–1591.

https://doi.org/10.1042/BCJ20160085

Published: 27 May 2016

... mutagenesis and transcriptional and functional assays, we identify a community of residues from the JH2 helix αC, SH2-JH2 linker and JH1 kinase domain that mediate V617F-induced activation. This circuit is broken by altering the charge of residues along the solvent-exposed face of the JH2 αC, which...

View article titled, Uncoupling JAK2 V617F activation from cytokine-induced signalling by modulation of JH2 αC helix

Includes: Supplementary data

Articles

The function of orthologues of the human Parkinson's disease gene LRRK2 across species: implications for disease modelling in preclinical research

Rebekah G. Langston, Iakov N. Rudenko, Mark R. Cookson

Biochem J (2016) 473 (3): 221–232.

https://doi.org/10.1042/BJ20150985

Published: 25 January 2016

...Rebekah G. Langston; Iakov N. Rudenko; Mark R. Cookson In the period since LRRK2 (leucine-rich repeat kinase 2) was identified as a causal gene for late-onset autosomal dominant parkinsonism, a great deal of work has been aimed at understanding whether the LRRK2 protein might be a druggable target...

View article titled, The function of orthologues of the human Parkinson's disease gene LRRK2 across species: implications for disease modelling in preclinical research

Articles

Nuclear protein kinase CLK1 uses a non-traditional docking mechanism to select physiological substrates

Malik M. Keshwani, Kendra L. Hailey, Brandon E. Aubol, Laurent Fattet, Maria L. McGlone, Patricia A. Jennings, Joseph A. Adams

Biochem J (2015) 472 (3): 329–338.

https://doi.org/10.1042/BJ20150903

Published: 27 November 2015

...Malik M. Keshwani; Kendra L. Hailey; Brandon E. Aubol; Laurent Fattet; Maria L. McGlone; Patricia A. Jennings; Joseph A. Adams Phosphorylation-dependent cell communication requires enzymes that specifically recognize key proteins in a sea of similar, competing substrates. The protein kinases...

View article titled, Nuclear protein kinase CLK1 uses a non-traditional docking mechanism to select physiological substrates

Articles

TOR signalling in plants

Daniel Rexin, Christian Meyer, Christophe Robaglia, Bruce Veit

Biochem J (2015) 470 (1): 1–14.

https://doi.org/10.1042/BJ20150505

Published: 06 August 2015

...Daniel Rexin; Christian Meyer; Christophe Robaglia; Bruce Veit Although the eukaryotic TOR (target of rapamycin) kinase signalling pathway has emerged as a key player for integrating nutrient-, energy- and stress-related cues with growth and metabolic outputs, relatively little is known of how...

View article titled, TOR signalling in plants

Articles

Crystal structure of human platelet phosphofructokinase-1 locked in an activated conformation

Marco Kloos, Antje Brüser, Jürgen Kirchberger, Torsten Schöneberg, Norbert Sträter

Biochem J (2015) 469 (3): 421–432.

https://doi.org/10.1042/BJ20150251

Published: 23 July 2015

... architecture. At different binding sites, effectors control enzyme activity by inducing allosteric changes at the dimer interface influencing binding of fructose-6-phosphate (F6P). allostery cancer co-operativity glycolysis kinase Tarui's disease 6-Phosphofructokinase (Pfk; EC 2.7.1.11...

View article titled, Crystal structure of human platelet phosphofructokinase-1 locked in an activated conformation

Includes: Supplementary data

Articles

LRRK2 dephosphorylation increases its ubiquitination

Jing Zhao, Tyler P. Molitor, J. William Langston, R. Jeremy Nichols

Biochem J (2015) 469 (1): 107–120.

https://doi.org/10.1042/BJ20141305

Published: 19 June 2015

...Jing Zhao; Tyler P. Molitor; J. William Langston; R. Jeremy Nichols Activating mutations in the leucine rich repeat protein kinase 2 ( LRRK2 ) gene are the most common cause of inherited Parkinson's disease (PD). LRRK2 is phosphorylated on a cluster of phosphosites including Ser 910 , Ser 935 , Ser...

View article titled, LRRK2 dephosphorylation increases its ubiquitination

Articles

The Tribbles 2 (TRB2) pseudokinase binds to ATP and autophosphorylates in a metal-independent manner

Fiona P. Bailey, Dominic P. Byrne, Krishnadev Oruganty, Claire E. Eyers, Christopher J. Novotny, Kevan M. Shokat, Natarajan Kannan, Patrick A. Eyers

Biochem J (2015) 467 (1): 47–62.

https://doi.org/10.1042/BJ20141441

Published: 20 March 2015

... 2015 Biochemical Society 2015 The human Tribbles (TRB)-related pseudokinases are CAMK (calcium/calmodulin-dependent protein kinase)-related family members that have evolved a series of highly unusual motifs in the ‘pseudocatalytic’ domain. In canonical kinases, conserved amino acids bind...

View article titled, The Tribbles 2 (TRB2) pseudokinase binds to ATP and autophosphorylates in a metal-independent manner

Includes: Supplementary data

Articles

Conserved proline-directed phosphorylation regulates SR protein conformation and splicing function

Malik M. Keshwani, Brandon E. Aubol, Laurent Fattet, Chen-Ting Ma, Jinsong Qiu, Patricia A. Jennings, Xiang-Dong Fu, Joseph A. Adams

Biochem J (2015) 466 (2): 311–322.

https://doi.org/10.1042/BJ20141373

Published: 20 February 2015

... in arginine–serine dipeptide repeats (RS domains). Although the SRPKs (SR-specific protein kinases) phosphorylate these repeats, RS domains also contain prolines with flanking serines that are phosphorylated by a second family of protein kinases known as the CLKs (Cdc2-like kinases). The role of specific...

View article titled, Conserved proline-directed phosphorylation regulates SR protein conformation and splicing function

Includes: Supplementary data

Articles

Going for broke: targeting the human cancer pseudokinome

Fiona P. Bailey, Dominic P. Byrne, Daniel McSkimming, Natarajan Kannan, Patrick A. Eyers

Biochem J (2015) 465 (2): 195–211.

https://doi.org/10.1042/BJ20141060

Published: 06 January 2015

...Fiona P. Bailey; Dominic P. Byrne; Daniel McSkimming; Natarajan Kannan; Patrick A. Eyers Protein phosphorylation lies at the heart of cell signalling, and somatic mutation(s) in kinases drives and sustains a multitude of human diseases, including cancer. The human protein kinase superfamily...

View article titled, Going for broke: targeting the human cancer pseudokinome

Articles

MEKK2 regulates paxillin ubiquitylation and localization in MDA-MB 231 breast cancer cells

Magdalene Ameka, Michael P. Kahle, Mathew Perez-Neut, Saverio Gentile, Ahmed A. Mirza, Bruce D. Cuevas

Biochem J (2014) 464 (1): 99–108.

https://doi.org/10.1042/BJ20140420

Published: 23 October 2014

...Magdalene Ameka; Michael P. Kahle; Mathew Perez-Neut; Saverio Gentile; Ahmed A. Mirza; Bruce D. Cuevas The intracellular kinase MEKK2 (mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase kinase 2) is an upstream regulator of JNK (c-Jun N-terminal kinase), but additional...

View article titled, MEKK2 regulates paxillin ubiquitylation and localization in MDA-MB 231 breast cancer cells

Includes: Supplementary data

Articles

The molecular regulation of Janus kinase (JAK) activation

Jeffrey J. Babon, Isabelle S. Lucet, James M. Murphy, Nicos A. Nicola, Leila N. Varghese

Biochem J (2014) 462 (1): 1–13.

https://doi.org/10.1042/BJ20140712

Published: 24 July 2014

...Jeffrey J. Babon; Isabelle S. Lucet; James M. Murphy; Nicos A. Nicola; Leila N. Varghese The JAK (Janus kinase) family members serve essential roles as the intracellular signalling effectors of cytokine receptors. This family, comprising JAK1, JAK2, JAK3 and TYK2 (tyrosine kinase 2), was first...

View article titled, The molecular regulation of Janus kinase (JAK) activation

Articles

N-terminus of the protein kinase CLK1 induces SR protein hyperphosphorylation

Brandon E. Aubol, Ryan M. Plocinik, Malik M. Keshwani, Maria L. McGlone, Jonathan C. Hagopian, Gourisankar Ghosh, Xiang-Dong Fu, Joseph A. Adams

Biochem J (2014) 462 (1): 143–152.

https://doi.org/10.1042/BJ20140494

Published: 24 July 2014

... families of protein kinases. The SRPKs (SR-specific protein kinases) efficiently phosphorylate the arginine/serine dipeptides in the RS domain using a conserved docking groove in the kinase domain. In contrast, CLKs (Cdc2-like kinases) lack a docking groove and phosphorylate both arginine/serine and serine...

View article titled, N-terminus of the protein kinase CLK1 induces SR protein hyperphosphorylation

Includes: Supplementary data

Articles

Cardioprotective 3′,4′-dihydroxyflavonol attenuation of JNK and p38 MAPK signalling involves CaMKII inhibition

Nicholas R. Lim, Colleen J. Thomas, Lokugan S. Silva, Yvonne Y. Yeap, Suwan Yap, James R. Bell, Lea M. D. Delbridge, Marie A. Bogoyevitch, Owen L. Woodman, Spencer J. Williams, Clive N. May, Dominic C. H. Ng

Biochem J (2013) 456 (2): 149–161.

https://doi.org/10.1042/BJ20121538

Published: 08 November 2013

...) injury. The biological activities of flavonols are associated with kinase modulation to alter cell signalling. We thus investigated the effects of DiOHF on the activation of MAPKs (mitogen-activated protein kinases) that regulate the cardiac stress response. In an ovine model of I/R, JNK (c-Jun N...

View article titled, Cardioprotective 3′,4′-dihydroxyflavonol attenuation of JNK and p38 MAPK signalling involves CaMKII inhibition

Includes: Supplementary data

Articles

A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery

Yinghong Gao, Stephen P. Davies, Martin Augustin, Anna Woodward, Umesh A. Patel, Robert Kovelman, Kevin J. Harvey

Biochem J (2013) 451 (2): 313–328.

https://doi.org/10.1042/BJ20121418

Published: 28 March 2013

...Yinghong Gao; Stephen P. Davies; Martin Augustin; Anna Woodward; Umesh A. Patel; Robert Kovelman; Kevin J. Harvey Despite the development of a number of efficacious kinase inhibitors, the strategies for rational design of these compounds have been limited by target promiscuity. In an effort...

View article titled, A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery

Includes: Supplementary data

Articles

An aminoquinazoline inhibitor of the essential bacterial cell wall synthetic enzyme GlmU has a unique non-protein-kinase-like binding mode

Nicholas A. Larsen, Tory J. Nash, Marshall Morningstar, Adam B. Shapiro, Camil Joubran, Carolyn J. Blackett, Arthur D. Patten, P. Ann Boriack-Sjodin, Peter Doig

Biochem J (2012) 446 (3): 405–413.

https://doi.org/10.1042/BJ20120596

Published: 28 August 2012

... biosynthesis GlmU high-throughput screening inhibitor kinase N -acetylglucosamine-1-phosphate uridyltransferase Inhibition of cell wall biosynthesis has been a successful approach for developing antibiotics. Both β-lactam-containing compounds and glycopeptides exploit this mode of action...

View article titled, An aminoquinazoline inhibitor of the essential bacterial cell wall synthetic enzyme GlmU has a unique non-protein-kinase-like binding mode

Includes: Supplementary data

Articles

Discovery of cellular substrates for protein kinase A using a peptide array screening protocol

F. Donelson Smith, Bret K. Samelson, John D. Scott

Biochem J (2011) 438 (1): 103–110.

https://doi.org/10.1042/BJ20110720

Published: 27 July 2011

...F. Donelson Smith; Bret K. Samelson; John D. Scott Post-translational modification of proteins is a universal form of cellular regulation. Phosphorylation on serine, threonine, tyrosine or histidine residues by protein kinases is the most widespread and versatile form of covalent modification...

View article titled, Discovery of cellular substrates for protein kinase A using a peptide array screening protocol

Includes: Supplementary data

Articles

How protein kinases co-ordinate mitosis in animal cells

Hoi Tang Ma, Randy Y. C. Poon

Biochem J (2011) 435 (1): 17–31.

https://doi.org/10.1042/BJ20100284

Published: 15 March 2011

...Hoi Tang Ma; Randy Y. C. Poon Mitosis is associated with profound changes in cell physiology and a spectacular surge in protein phosphorylation. To accomplish these, a remarkably large portion of the kinome is involved in the process. In the present review, we will focus on classic mitotic kinases...

View article titled, How protein kinases co-ordinate mitosis in animal cells

Articles

Connexin43 phosphorylation: structural changes and biological effects

Joell L. Solan, Paul D. Lampe

Biochem J (2009) 419 (2): 261–272.

https://doi.org/10.1042/BJ20082319

Published: 27 March 2009

... channel gating and connexin degradation. Consistent with a short (1–5 h) protein half-life, connexin43 phosphorylation is dynamic and changes in response to activation of many different kinases. The present review assesses our current understanding of the effects of phosphorylation on connexin43 structure...

View article titled, Connexin43 phosphorylation: structural changes and biological effects

Includes: Multimedia, Supplementary data

Articles

Phosphorylation of cardiac troponin I by mammalian sterile 20-like kinase 1

Bei You, Guijun Yan, Zhiling Zhang, Lin Yan, Jing Li, Qingyuan Ge, Jian-Ping Jin, Jianxin Sun

Biochem J (2009) 418 (1): 93–101.

https://doi.org/10.1042/BJ20081340

Published: 28 January 2009

...Bei You; Guijun Yan; Zhiling Zhang; Lin Yan; Jing Li; Qingyuan Ge; Jian-Ping Jin; Jianxin Sun Mst1 (mammalian sterile 20-like kinase 1) is a ubiquitously expressed serine/threonine kinase and its activation in the heart causes cardiomyocyte apoptosis and dilated cardiomyopathy. Its myocardial...

View article titled, Phosphorylation of cardiac troponin I by mammalian sterile 20-like kinase 1

Includes: Supplementary data

Articles

Phosphoregulation of human Mps1 kinase

Rebecca K. Tyler, Matthew L. H. Chu, Hannah Johnson, Edward A. McKenzie, Simon J. Gaskell, Patrick A. Eyers

Biochem J (2009) 417 (1): 173–184.

https://doi.org/10.1042/BJ20081310

Published: 12 December 2008

...Rebecca K. Tyler; Matthew L. H. Chu; Hannah Johnson; Edward A. McKenzie; Simon J. Gaskell; Patrick A. Eyers The dual-specificity protein kinase Mps1 (monopolar spindle 1) is a phosphoprotein required for error-free mitotic progression in eukaryotes. In the present study, we have investigated human...

View article titled, Phosphoregulation of human Mps1 kinase

Includes: Supplementary data

Articles

LKB1: cancer, polarity, metabolism, and now fertility

Reuben J. Shaw

Biochem J (2008) 416 (1): e1–e3.

https://doi.org/10.1042/BJ20082023

Published: 28 October 2008

...Reuben J. Shaw The LKB1 serine/threonine kinase is a tumour suppressor responsible for the inherited familial cancer disorder Peutz-Jeghers syndrome and is inactivated in a large percentage of human lung cancers. LKB1 acts a master kinase, directly phosphorylating and activating a family of 14 AMPK...

View article titled, LKB1: cancer, polarity, metabolism, and now fertility

Articles

Identification and characterization of FUS/TLS as a new target of ATM

Mary Gardiner, Rachel Toth, Franck Vandermoere, Nicholas A. Morrice, John Rouse

Biochem J (2008) 415 (2): 297–307.

https://doi.org/10.1042/BJ20081135

Published: 25 September 2008

...Mary Gardiner; Rachel Toth; Franck Vandermoere; Nicholas A. Morrice; John Rouse ATM (ataxia-telangiectasia mutated), ATR (ATM- and Rad3-related) and DNA-PK (DNA-dependent protein kinase), important regulators of genome stability, belong to the PIKK (phosphoinositide 3-kinase-like kinase) family...

View article titled, Identification and characterization of FUS/TLS as a new target of ATM

Articles

Stabilizing daily clock proteins

Hugh D. Piggins

Biochem J (2006) 399 (1): e1.

https://doi.org/10.1042/BJ20061211

Published: 13 September 2006

... products of the clock genes. Kinases play key roles in regulating clock function. For example, activation of the MAPK (mitogen-activated protein kinase) pathway in SCN neurons is important for resetting of this circadian clock via light stimulation of the retina [ 6 ]. Furthermore, CK1ϵ (casein kinase 1ϵ...

View article titled, Stabilizing daily clock proteins

Articles

Regulation of ERK1 gene expression by coactivator proteins

Beanca Y. Chu, Kim Tran, Tony K. S. Ku, David L. Crowe

Biochem J (2005) 392 (3): 589–599.

https://doi.org/10.1042/BJ20050542

Published: 06 December 2005

...Beanca Y. Chu; Kim Tran; Tony K. S. Ku; David L. Crowe RARs (retinoic acid receptors) mediate the effect of their ligand RA (retinoic acid) on gene expression. We previously showed that RA inhibited cellular proliferation in part by decreasing expression of the mitogen activated protein kinase ERK1...

View article titled, Regulation of ERK1 gene expression by coactivator proteins

Articles

A proteolytic fragment of Mcl-1 exhibits nuclear localization and regulates cell growth by interaction with Cdk1

Sarwat JAMIL, Rafat SOBOUTI, Payman HOJABRPOUR, Meera RAJ, Juergen KAST, Vincent DURONIO

Biochem J (2005) 387 (3): 659–667.

https://doi.org/10.1042/BJ20041596

Published: 26 April 2005

.... In the present study, we show a cell-cycle-regulatory role of Mcl-1 involving a shortened form of the Mcl-1 polypeptide, primarily localized to the nucleus, which we call snMcl-1. snMcl-1 interacts with the cell-cycle-regulatory protein Cdk1 (cyclin-dependent kinase 1; also known as cdc2) in the nucleus...

View article titled, A proteolytic fragment of Mcl-1 exhibits nuclear localization and regulates cell growth by interaction with Cdk1

Articles

Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors

Stanley F. BARNETT, Deborah DEFEO-JONES, Sheng FU, Paula J. HANCOCK, Kathleen M. HASKELL, Raymond E. JONES, Jason A. KAHANA, Astrid M. KRAL, Karen LEANDER, Ling L. LEE, John MALINOWSKI, Elizabeth M. McAVOY, Debbie D. NAHAS, Ronald G. ROBINSON, Hans E. HUBER

Biochem J (2005) 385 (2): 399–408.

https://doi.org/10.1042/BJ20041140

Published: 07 January 2005

... (homogeneous time-resolved fluorescence) assay for Akt kinase activity and screened approx. 270000 compounds for their ability to inhibit the three isoforms of Akt. Two Akt inhibitors were identified that exhibited isoenzyme specificity. The first compound (Akt-I-1) inhibited only Akt1 (IC 50 4.6 μM) while...

View article titled, Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors

Articles

Two conserved cysteine residues are critical for the enzymic function of the human platelet-derived growth factor receptor-β: evidence for different roles of Cys-822 and Cys-940 in the kinase activity

Joon-Won LEE, Jee-Eun KIM, Eun-Jung PARK, Jin-Hyun KIM, Chang-Hun LEE, Seung-Rock LEE, Jongbum KWON

Biochem J (2004) 382 (2): 631–639.

https://doi.org/10.1042/BJ20040624

Published: 24 August 2004

... in the enzymic function of PDGFR-β. We found that N -ethylmaleimide, which selectively alkylates free thiol groups of cysteine residues, completely inhibited the kinase activity of PDGFR-β. We then identified, through site-directed mutagenesis, two conserved cysteine residues critical for the enzymic function...

View article titled, Two conserved cysteine residues are critical for the enzymic function of the human platelet-derived growth factor receptor-β: evidence for different roles of Cys-822 and Cys-940 in the kinase activity

Articles

Protein kinase function and glutathionylation

Anthony N. ANSELMO, Melanie H. COBB

Biochem J (2004) 381 (3): e1.

https://doi.org/10.1042/BJ20040873

Published: 27 July 2004

.... As an antioxidant, glutathione serves in maintaining the reduced state of cellular protein thiol groups. The paper by Cross and Templeton appearing in this issue of the Biochemical Journal describes a mechanism by which glutathionylation plays a key role in the regulation of the kinase activity of MEKK1 [MAP...

View article titled, Protein kinase function and glutathionylation

Articles

Activated Src increases adhesion, survival and alpha2-integrin expression in human breast cancer cells

Hee Boong PARK, Vita GOLUBOVSKAYA, Lihui XU, Xihui YANG, Jin Woo LEE, Sean SCULLY, II, Rolf Joseph CRAVEN, William G. CANCE

Biochem J (2004) 378 (2): 559–567.

https://doi.org/10.1042/bj20031392

Published: 01 March 2004

...Hee Boong PARK; Vita GOLUBOVSKAYA; Lihui XU; Xihui YANG; Jin Woo LEE; Sean SCULLY, II; Rolf Joseph CRAVEN; William G. CANCE Focal adhesion kinase (FAK) is an intracellular kinase that localizes to focal adhesions. FAK is overexpressed in human tumours, and FAK regulates both cellular adhesion...

View article titled, Activated Src increases adhesion, survival and alpha2-integrin expression in human breast cancer cells

Articles

Role for AMP-activated protein kinase in glucose-stimulated insulin secretion and preproinsulin gene expression

Gabriela da SILVA XAVIER, Isabelle LECLERC, Aniko VARADI, Takashi TSUBOI, S. Kelly MOULE, Guy A. RUTTER

Biochem J (2003) 371 (3): 761–774.

https://doi.org/10.1042/bj20021812

Published: 01 May 2003

...Gabriela da SILVA XAVIER; Isabelle LECLERC; Aniko VARADI; Takashi TSUBOI; S. Kelly MOULE; Guy A. RUTTER AMP-activated protein kinase (AMPK) has recently been implicated in the control of preproinsulin gene expression in pancreatic islet β-cells [da Silva Xavier, Leclerc, Salt, Doiron, Hardie, Kahn...

View article titled, Role for AMP-activated protein kinase in glucose-stimulated insulin secretion and preproinsulin gene expression

Articles

Positive and negative regulation of T-cell activation through kinases and phosphatases

Tomas MUSTELIN, Kjetil TASKÉN

Biochem J (2003) 371 (1): 15–27.

https://doi.org/10.1042/bj20021637

Published: 01 April 2003

...Tomas MUSTELIN; Kjetil TASKÉN The sequence of events in T-cell antigen receptor (TCR) signalling leading to T-cell activation involves regulation of a number of protein tyrosine kinases (PTKs) and the phosphorylation status of many of their substrates. Proximal signalling pathways involve PTKs...

View article titled, Positive and negative regulation of T-cell activation through kinases and phosphatases

Articles

Phosphorylation is a regulatory mechanism in apolipoprotein B mRNA editing

Zhigang CHEN, Thomas L. EGGERMAN, Amy P. PATTERSON

Biochem J (2001) 357 (3): 661–672.

https://doi.org/10.1042/bj3570661

Published: 25 July 2001

...Zhigang CHEN; Thomas L. EGGERMAN; Amy P. PATTERSON The editing of apolipoprotein B (apoB) mRNA is under tissue-specific, developmental and metabolic regulation. We found that multiple protein kinase inhibitors or activators increased apoB mRNA editing up to 2.5-fold in Caco-2 cells and 3–8-fold...

View article titled, Phosphorylation is a regulatory mechanism in apolipoprotein B mRNA editing

Articles

Synapsins as major neuronal Ca 2+ /S100A1-interacting proteins

Jörg HEIERHORST, Ken I. MITCHELHILL, Richard J. MANN, Tony TIGANIS, Andrew J. CZERNIK, Paul GREENGARD, Bruce E. KEMP

Biochem J (1999) 344 (2): 577–583.

https://doi.org/10.1042/bj3440577

Published: 24 November 1999

...Jörg HEIERHORST; Ken I. MITCHELHILL; Richard J. MANN; Tony TIGANIS; Andrew J. CZERNIK; Paul GREENGARD; Bruce E. KEMP The mammalian S100A1 protein can activate the invertebrate myosin-associated giant protein kinase twitchin in a Ca 2+ -dependent manner by more than 1000-fold in vitro ; however...

View article titled, Synapsins as major neuronal Ca 2+ /S100A1-interacting proteins

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