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Keywords: kinase
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Articles
Biochem J (2023) 480 (2): 141–160.
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...
Includes: Multimedia, Supplementary data
Articles
Biochem J (2022) 479 (1): 1–22.
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...
Articles
Biochem J (2021) 478 (19): 3555–3573.
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...
Includes: Supplementary data
Articles
Biochem J (2021) 478 (3): 553–578.
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...
Includes: Supplementary data
Articles
Biochem J (2020) 477 (1): 275–284.
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...
Includes: Supplementary data
Articles
Biochem J (2019) 476 (21): 3197–3209.
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...
Includes: Supplementary data
Articles
Biochem J (2019) 476 (7): 1037–1051.
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...
Includes: Supplementary data
Articles
Biochem J (2019) 476 (3): 559–579.
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...
Includes: Supplementary data
Articles
Biochem J (2018) 475 (15): 2417–2433.
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...
Includes: Supplementary data
Articles
Biochem J (2018) 475 (11): 1861–1883.
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...
Includes: Supplementary data
Articles
Biochem J (2018) 475 (1): 329–340.
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...
Includes: Supplementary data
Articles
Biochem J (2017) 474 (15): 2585–2599.
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...
Includes: Supplementary data
Articles
Biochem J (2017) 474 (9): 1439–1451.
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...
Articles
Biochem J (2017) 474 (5): 699–713.
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...
Includes: Supplementary data
Articles
Biochem J (2017) 474 (4): 493–515.
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...
Includes: Supplementary data
Articles
Biochem J (2017) 474 (3): 385–398.
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...
Includes: Supplementary data
Articles
Biochem J (2016) 473 (11): 1579–1591.
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...
Includes: Supplementary data
Articles
Biochem J (2016) 473 (3): 221–232.
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...
Articles
Biochem J (2015) 472 (3): 329–338.
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...
Articles
Biochem J (2015) 470 (1): 1–14.
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...
Articles
Biochem J (2015) 469 (3): 421–432.
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...
Includes: Supplementary data
Articles
Biochem J (2015) 469 (1): 107–120.
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...
Articles
Biochem J (2015) 467 (1): 47–62.
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...
Includes: Supplementary data
Articles
Biochem J (2015) 466 (2): 311–322.
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...
Includes: Supplementary data
Articles
Biochem J (2015) 465 (2): 195–211.
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...
Articles
Biochem J (2014) 464 (1): 99–108.
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...
Includes: Supplementary data
Articles
Biochem J (2014) 462 (1): 143–152.
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...
Includes: Supplementary data
Articles
Biochem J (2014) 462 (1): 1–13.
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...
Articles
Biochem J (2013) 456 (2): 149–161.
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...
Includes: Supplementary data
Articles
Biochem J (2013) 451 (2): 313–328.
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...
Includes: Supplementary data
Articles
Biochem J (2012) 446 (3): 405–413.
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...
Includes: Supplementary data
Articles
Biochem J (2011) 438 (1): 103–110.
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...
Includes: Supplementary data
Articles
Biochem J (2011) 435 (1): 17–31.
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...
Articles
Biochem J (2009) 419 (2): 261–272.
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...
Includes: Multimedia, Supplementary data
Articles
Biochem J (2009) 418 (1): 93–101.
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...
Includes: Supplementary data
Articles
Biochem J (2009) 417 (1): 173–184.
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...
Includes: Supplementary data
Articles
Biochem J (2008) 416 (1): e1–e3.
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...
Articles
Biochem J (2008) 415 (2): 297–307.
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...
Articles
Biochem J (2006) 399 (1): e1.
Published: 13 September 2006
...). 1 email hugh.piggins@manchester.ac.uk 8 8 2006 11 8 2006 14 8 2006 The Biochemical Society, London 2006 circadian clock clock gene protein Drosophila kinase Neurospora phosphatase Biological clocks are endogenous timekeeping mechanisms present in both...
Articles
Biochem J (2005) 392 (3): 589–599.
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...
Articles
Biochem J (2005) 387 (3): 659–667.
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...
Articles
Biochem J (2005) 385 (2): 399–408.
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...
Articles
Biochem J (2004) 382 (2): 631–639.
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...
Articles
Biochem J (2004) 381 (3): e1.
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...
Articles
Biochem J (2004) 378 (2): 559–567.
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...
Articles
Biochem J (2003) 371 (3): 761–774.
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...
Articles
Biochem J (2003) 371 (1): 15–27.
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...
Articles
Biochem J (2001) 357 (3): 661–672.
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...
Articles
Biochem J (1999) 344 (2): 577–583.
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...
Articles
Biochem J (1999) 342 (1): 133–141.
Published: 10 August 1999
...-protein interactions and indicate that some human cancers might have amplified one or more Ser 20 and Thr 18 kinase signalling cascades to modulate p53 activity. 1 To whom correspondence should be addressed (e-mail t.r.hupp@dundee.ac.uk). 2 11 1998 4 5 1999 2 6 1999...