Reviews are in pink.

Cancer-associated mutations in protein kinase C theta are loss-of-function
Hodapp SJ, Gravel N, Kannan N, Newton AC
Biochemical Journal, (2024) 481: 759-775. PDF

Post-translational modification-centric base editor screens to assess phosphorylation site functionality in high throughput
Kennedy PH, Alborzian Deh Sheikh A, Balakar M, Jones AC, Olive ME, Hegde M, Matias MI, Pirete N, Burt R, Levy J, Little T, Hogan PG, Liu DR, Doench JG, Newton AC, Gottschalk RA, de Boer CG, Alarcón S, Newby GA, Myers SA
Nature Methods, (2024) LINK

Sensitive Fluorescent Biosensor Reveals Differential Subcellular Regulation of PKC
Su Q, Zhang J, Lin W, Zhang JF, Newton AC, Mehta S, Yang J, Zhang J
BioRxiv, (2024) PDF

Fructose-1,6-bisphosphatase is a nonenzymatic safety valve that curtails AKT activation to prevent insulin hyperresponsiveness.
Gu L, Zhu Y, Watari K, Lee M, Liu J, Perez S, Thai M, Mayfield J, Zhang B, Cunha e Rocha K, Li F, Kim L, Jones AC, Wierzbicki IH, Liu X, Newton AC, Kisseleva T, Lee JH, Ying W, Gonzalez DJ, Saltiel A, Simon MC, Karin M.
Cell Metabolism 35 (6) 1009-1021 (2023). PDF

Single-residue mutation in protein kinase C toggles between cancer and neurodegeneration.
Jones AC, Kornev AP, Weng J, Manning G, Taylor SS, Newton AC.
Biochemical Journal, (2023). PDF

Protein Kinase C showcases allosteric control: activation of LRRK1.
Tovell H, Newton AC.
Biochemical Journal, (2023). PDF

“PHLPP Signaling in Immune Cells” PI3K and AKT Isoforms in Immunity: Mechanisms and Therapeutic Opportunities.
Lordén G, Lam AJ, Levings MK, Newton AC.
Springer International Publishing 117-143 (2022). PDF

Enhanced activity of Alzheimer disease-associated variant of protein kinase Cα drives cognitive decline in a mouse model.
Lordén G, Wozniak JM, Doré K, Dozier LE, Cates-Gatto C, Patrick GN, Gonzalez DJ, Roberts AJ, Tanzi RE, Newton AC.
Nature Communications 13, 7200 (2022). PDF

Mutations in protein kinase Cγ promote spinocerebellar ataxia type 14 by impairing kinase autoinhibition.
Pilo CA, Baffi TR, Kornev AP, Kunkel MT, Malfavon M, Chen D, Rossitto L, Chen DX, Huang L, Longman C, Kannan N, Raskind WH, Gonzalez DJ, Taylor SS, Gorrie G, Newton AC.
Science Signaling, (2022), Vol. 15, Issue 753. PDF

Two Sides of the Same Coin: Protein Kinase C γ in Cancer and Neurodegeneration
Pilo CA, Newton AC.
Frontiers in Cell and Developmental Biology, (2022);10:929510. PDF

Protein kinase C: release from quarantine by mTORC2
Baffi TR, Newton AC.
Trends in Biochemical Sciences, (2022), Vol. 47, No. 6. PDF

Conventional protein kinase C in the brain: repurposing cancer drugs for neurodegenerative treatment?
Lordén G, Newton AC.
Neuronal Signaling (2021) 5 (4): NS20210036.  PDF

mTORC2 controls the activity of PKC and Akt by phosphorylating a conserved TOR interaction motif.
Baffi TR, Lordén G, Wozniak JM, Feichtner A, Yeung W, Kornev AP, King CC, Del Rio JC, Limaye AJ, Bogomolovas J, Gould CM, Chen J, Kennedy EJ, Kannan N, Gonzalez DJ, Stefan E, Taylor SS, Newton AC.
Sci. Signal. 14, eabe4509 (2021). PDF

Protein Kinase C.
Newton AC.
Encyclopedia of Molecular Pharmacology. (2021) https://doi.org/10.1007/978-3-030-21573-6_199-1. PDF

PKCα Is Recruited to Staphylococcus aureus-Containing Phagosomes and Impairs Bacterial Replication by Inhibition of Autophagy.
Gauron MC, Newton AC, Colombo MI.
Front. Immunol. (2021) 12:662987. PDF

Protein kinase C fusion proteins are paradoxically loss-of function in cancer.
Van AN, Kunkel MT, Baffi TR, Lordén G, Antal CE, Banerjee S, Newton AC.
Journal of Biological Chemistry (2021). PDF

PHLPPing the balance: restoration of protein kinase C in cancer
Tovell H, Newton AC.
Biochem J (2021) 478 (2): 341–355. PDF

Pharmacology on Target.
Kawashima AT, Newton AC.
Trends Pharmacol Sci. (2020);41(4):227-230.  PDF

PHLPP1 counter-regulates STAT1-mediated inflammatory signaling.
Katsenelson KC, Stender JD, Kawashima AT, Lordén G, Uchiyama S, Nizet V, Glass CK, Newton AC.
Elife. (2019);8. pii: e48609. PDF

Protein kinases in tune.
Newton AC.
IUBMB Life. (2019);71(6):670-671. PDF

The PHLPP2 phosphatase is a druggable driver of prostate cancer progression.
Nowak DG, Katsenelson KC, Watrud KE, Chen M, Mathew G, D’Andrea VD, Lee
MF, Swamynathan MM, Casanova-Salas I, Jibilian MC, Buckholtz CL,
Ambrico AJ, Pan CH, Wilkinson JE, Newton AC, Trotman LC.
J Cell Biol. (2019);218(6):1943-1957. PDF

Protein Kinase C Quality Control by Phosphatase PHLPP1 Unveils Loss-of-Function Mechanism in Cancer.
Baffi TR, Van AN, Zhao W, Mills GB, Newton AC.
Mol Cell. (2019);74(2):378-392. PDF

Apical-basal polarity inhibits epithelial-mesenchymal transition and tumour
metastasis by PAR-complex-mediated SNAI1 degradation.
Jung HY, Fattet L, Tsai JH, Kajimoto T, Chang Q, Newton AC, Yang J.
Nat Cell Biol. 2019 Mar;21(3):359-371. PDF

Activation of atypical protein kinase C by sphingosine 1-phosphate revealed by an aPKC-specific activity reporter.
Kajimoto T, Caliman AD, Tobias IS, Okada T, Pilo CA, Van AN, Andrew McCammon J, Nakamura SI, Newton AC.
Sci Signal. 2019 Jan 1;12(562). PDF

Protein kinase Cα gain-of-function variant in
Alzheimer’s disease displays enhanced catalysis by a mechanism that
evades down-regulation.
Callender JA, Yang Y, Lordén G, Stephenson NL, Jones AC, Brognard J, Newton AC.
Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):E5497-E5505. PDF

Genetic code expansion and live cell imaging reveal
that Thr308 phosphorylation is irreplaceable and sufficient for Akt1 activity.
Balasuriya N, Kunkel MT, Liu X, Biggar KK, Li SS, Newton AC, O’Donoghue P.
J Biol Chem. 2018 Jul 6;293(27):10744-10756. PDF

Integrative annotation and knowledge discovery
of kinase post-translational modifications and cancer-associated
mutations through federated protein ontologies and resources.
Huang LC, Ross KE, Baffi TR, Drabkin H, Kochut KJ, Ruan Z, D’Eustachio P,
McSkimming D, Arighi C, Chen C, Natale DA, Smith C, Gaudet P, Newton
AC, Wu C, Kannan N.
Sci Rep 2018 Apr 25;8:6518. PDF

Protein kinase C: perfectly balanced.
Newton AC.
Crit Rev Biochem Mol Biol. 2018 Apr;53(2):208-230. PDF

Protein Kinase C as a Tumor Suppressor.
Newton AC.
Semin Cancer Biol. 2018 Feb;48:18-26. PDF

Conventional protein kinase C in the brain: 40 years later.
Callender JA, Newton AC.
Neuronal Signaling. 2017 Apr 10;1(2):NS20160005. PDF

Reversing the Paradigm: Protein Kinase C as a Tumor Suppressor.
Newton AC, Brognard J.
Trends Pharmacol Sci. 2017 May;38(5):438-447. PDF

Protein Kinase C (Prkc).
Newton AC.
Encyclopedia of Signaling Molecules. 2017 Jan 2. PDF

PH Domain Leucine-Rich Repeat Protein Phosphatase (PHLPP).
Grzechnik AT, Newton AC.
Encyclopedia of Signaling Molecules. 2016 Dec 21. PDF

PHLPPing through history: a decade in the life of PHLPP phosphatases.
Grzechnik AT, Newton AC.
Biochem Soc Trans. 2016 Dec 15;44(6):1675-1682. PDF

KinView: a visual comparative sequence analysis tool for integrated kinome research.
McSkimming DI, Dastgheib S, Baffi TR, Byrne DP, Ferries S, Scott ST, Newton AC, Eyers CE, Kochut KJ, Eyers PA, Kannan N.
Mol Biosyst. 2016 Nov 15;12(12):3651-3665. PDF

Protein kinase C mechanisms that contribute to cardiac remodelling.
Newton AC, Antal CE, Steinberg SF.
Clin Sci (Lond). 2016 Sep 1;130(17):1499-510. PDF

Second Messengers
Newton AC, Bootman MD, and Scott JD.
Cold Spring Harb Perspect Biol. 2016 Aug. PDF

Bacterial spore coat protein kinases: A new twist to an old story.
Scott JD, Newton AC.
Proc Natl Acad Sci U S A. 2016 Jun 21;113(25):6811-2. PDF

Natural product anacardic acid from cashew nut shells stimulates neutrophil
extracellular trap production and bactericidal activity.
Hollands A, Corriden R, Gysler G, Dahesh S, Olson J, Ali SR, Kunkel MT,
Lin AE, Forli S, Newton AC, Kumar GB, Nair BG, Perry JJ, Nizet V.
J Biol Chem. 2016 Jul 1;291(27):13964-73. PDF

Protein scaffolds control localized protein kinase C ζ Activity.
Tobias IS, Newton AC.
J Biol Chem. 2016 Jun 24;291(26):13809-22. PDF

Gain-of-function mutations in protein kinase Cα (PKCα) may promote synaptic defects in Alzheimer’s disease.
Alfonso SI, Callender JA, Hooli B, Antal CE, Mullin K, Sherman MA,
Lesné SE, Leitges M, Newton AC, Tanzi RE, Malinow R.
Sci Signal. 2016 May 10;9(427):ra47. PDF

Protein kinase C beta II suppresses colorectal cancer by regulating IGF-1 mediated cell survival.
Dowling CM, Phelan J, Callender JA, Cathcart MC, Mehigan B, McCormick P, Dalton T, Coffey JC, Newton AC, O’Sullivan J, Kiely PA.
Oncotarget 2016 Mar 12;DOI:10.18632/oncotarget.8062. PDF

Protein kinase Cζ exhibits constitutive phosphorylation and phosphatidylinositol-3,4,5-triphosphate-independent regulation.
Tobias IS, Kaulich M, Kim PK, Simon N, Jacinto E, Dowdy SF, King CC, Newton AC.
Biochem J. 2016 Feb 15;473(4):509-23. PDF

Intramolecular C2 Domain-Mediated Autoinhibition of Protein Kinase C βII.
Antal CE, Callender JA, Kornev AP, Taylor SS, Newton AC.
Cell Rep. 2015 Aug 25;12(8):1252-60. PDF

Zeta Inhibitory Peptide Disrupts Electrostatic Interactions That Maintain
Atypical Protein Kinase C in Its Active Conformation on the Scaffold p62.
Tsai LC, Xie L, Dore K, Xie L, Del Rio JC, King CC, Martinez-Ariza G, Hulme C, Malinow R, Bourne PE, Newton AC.
J Biol Chem. 2015 Sep 4;290(36):21845-56. PDF

Deletion of the PH-domain and Leucine-rich Repeat Protein Phosphatase 1 (Phlpp1)
Increases Fibroblast Growth Factor (Fgf) 18 Expression and Promotes
Chondrocyte Proliferation.
Bradley EW, Carpio LR, Newton AC, Westendorf JJ.
J Biol Chem. 2015 Jun 26;290(26):16272-80. PDF

Multimodular biosensors reveal a novel platform for activation of G proteins by growth factor receptors.
Midde KK, Aznar N, Laederich MB, Ma GS, Kunkel MT, Newton AC, Ghosh P.
Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):E937-46. PDF

Cancer-Associated Protein Kinase C Mutations Reveal Kinase’s Role as Tumor Suppressor.
Antal CE, Hudson AM, Kang E, Zanca C, Wirth C, Stephenson NL, Trotter EW, Gallegos LL, Miller CJ, Furnari FB, Hunter T, Brognard J, Newton AC.
Cell. 2015 Jan 29;160(3):489-502. PDF

Protein Kinase D Inhibitors Uncouple Phosphorylation from Activity by Promoting Agonist-Dependent Activation Loop Phosphorylation.
Kunkel MT, Newton AC.
Chem Biol. 2015 Jan 22;22(1):98-106. PDF

Tuning the signalling output of protein kinase C.
Antal CE, Newton AC.
Biochem Soc Trans. 2014 Dec 1;42(6):1477-83. PDF

Pleckstrin homology domain leucine-rich repeat protein phosphatases set the amplitude of receptor tyrosine kinase output.
Reyes G, Niederst M, Cohen-Katsenelson K, Stender JD, Kunkel MT, Chen
M, Brognard J, Sierecki E, Gao T, Nowak DG, Totman LC, Glass CK, Newton
AC.
Proc Natl Acad Sci U S A. 2014 Sep 23;111(38):E3957-65. PDF

Biochemical Characterization of the Phosphatase Domain of the Tumor Suppressor PH
Domain Leucine-Rich Repeat Protein Phosphatase (PHLPP).
Sierecki E and Newton AC.
Biochemistry. 2014 Jun 3;53(24):3971–3981. PDF

Both Decreased and Increased SRPK1 Levels Promote Cancer by Interfering with PHLPP-Mediated Dephosphorylation of Akt.
Wang P, Zhou Z, Hu A, Ponte de Albuquerque C, Zhou Y, Hong L, Sierecki
E, Ajiro M, Kruhlak M, Harris C, Guan KL, Zheng ZM, Newton AC, Sun P,
Zhou H, Fu XD.
Mol Cell. 2014 May 8;54(3):378-91. PDF

Intramolecular Conformational Changes Optimize Protein Kinase C Signaling.
Antal CE, Violin JD, Kunkel MT, Skovsø S, Newton AC.
Chem Biol. 2014 Apr 24;21(4):459-69. PDF

Protein Kinase Cδ-Mediated Phosphorylation of Connexin43 Gap Junction Channels
Causes Movement within Gap Junctions followed by Vesicle
Internalization and Protein Degradation.
Cone AC, Cavin G, Ambrosi C, Hakozaki H, Wu-Zhang AX, Kunkel MT, Newton AC, Sosinsky GE.
J Biol Chem. 2014 Mar 28;289(13):8781–8798. PDF

Turning Off AKT: PHLPP as a Drug Target.
Newton AC, Trotman LC.
Annu Rev Pharmacol Toxicol. 2014 Jan 6;54:537-58. PDF

Imaging kinase activity at protein scaffolds.
Kunkel MT, Newton AC.
Methods Mol Biol. 2014;1071:129-37. PDF

Spatiotemporal dynamics of phosphorylation in lipid second messenger signaling.
Antal CE, Newton AC.
Mol Cell Proteomics. 2013 Dec;12(12):3498-508. PDF

Protein kinase C pharmacology: refining the toolbox.
Wu-Zhang AX, Newton AC.
Biochem J. 2013 Jun 1;452(2):195-209. PDF

Electrostatic and Hydrophobic Interactions Differentially Tune Membrane Binding Kinetics of the C2 Domain of Protein Kinase Cα.
Scott AM, Antal CE, Newton AC.
J Biol Chem. 2013 Jun 7;288(23):16905-15. PDF

Protein Kinase C Family.
Newton AC.
In The Encyclopedia of Biological Chemistry, Lennarz, W.J. and
Lane, M.D. (eds.) 2013;Vol 3:637-640. Waltham, MA: Academic Press.

Suppression of Survival Signalling Pathways by the Phosphatase PHLPP.
O’Neill AK, Niederst MJ, Newton AC.
FEBS J. 2013 Jan;280(2):572-583. PDF

Isozyme-specific Interaction of Protein Kinase Cδ with Mitochondria Dissected Using Live Cell Fluorescence Imaging.
Wu-Zhang AX, Murphy AN, Bachman M, Newton AC.
J Biol Chem. 2012 Nov 2;287(45):37891-906. PDF

Euphohelioscopin A Is a PKC Activator Capable of Inducing Macrophage Differentiation.
de Lichtervelde L, Antal CE, Boitano AE, Wang Y, Krastel P, Petersen F, Newton AC, Cooke MP, Schultz PG.
Chem Biol. 2012 Aug 24;19(8):994-1000. PDF

Shedding light on local kinase activation.
Scott JD and Newton AC.
BMC Biology 2012, 10:61 PDF

Imaging Oscillations of Protein Kinase C Activity in Cells
Kunkel MT and Newton AC.
In Protein Kinase Technologies, Neuromethods (Springer) 2012:251-257. PDF

Cellular pharmacology of protein kinase Mζ (PKMζ) contrasts with its in vitro profile: implications for PKMζ as a mediator of memory.
Wu-Zhang AX, Schramm CL, Nabavi S, Malinow R, Newton AC.
J Biol Chem. 2012 Apr 13;287(16):12879-85. PDF

The peptidyl-prolyl isomerase Pin1 controls the down-regulation of conventional protein kinase C isozymes.
Abrahamsen H, O’Neill AK, Kannan N, Kruse N, Taylor SS, Jennings PA, Newton AC.
J Biol Chem. 2012 Apr 13;287(16):13262-78. PDF

Mechanisms and Consequences of the Loss of PHLPP1 Phosphatase in Chronic Lymphocytic Leukemia (CLL).
O’Hayre M, Niederst M, Fecteau JF, Nguyen VM, Kipps TJ, Messmer D, Newton AC, Handel TM.
Leukemia. 2012 Jul;26(7):1689-92. PDF

PH domain Leucine-rich Repeat Protein Phosphatase, PHLPP: a New Player in Cell Signaling.
Warfel NA, Newton AC.
J Biol Chem. 2011 Dec 5. PDF

Protein Kinase Cα Promotes Cell Migration through a PDZ-Dependent Interaction
with its Novel Substrate Discs Large Homolog 1 (DLG1).
O’Neill AK, Gallegos LL, Justilien V, Garcia EL, Leitges M, Fields AP, Hall RA, Newton AC.
J Biol Chem. 2011 Dec 16;286(50):43559-68. PDF

Disruption of the Interface between the Pleckstrin Homology (PH) and Kinase
Domains of Akt Protein Is Sufficient for Hydrophobic Motif Site
Phosphorylation in the Absence of mTORC2.
Warfel NA, Niederst M, Newton AC.
J Biol Chem. 2011 Nov 11;286(45):39122-9. PDF

Genetically encoded fluorescent reporters to visualize protein kinase C activation in live cells.
Gallegos LL, Newton AC.
Methods Mol Biol. 2011;756:295-310. PDF

Identification of PHLPP1 as a Tumor Suppressor Reveals the Role of Feedback Activation in PTEN-Mutant Prostate Cancer Progression.
Chen M, Pratt CP, Zeeman
ME, Schultz N, Taylor BS, O’Neill A, Castillo-Martin M, Nowak DG, Naguib
A, Grace DM, Murn J, Navin N, Atwal GS, Sander C, Gerald WL,
Cordon-Cardo C, Newton AC, Carver BS, Trotman LC.
Cancer Cell. 2011 Aug 16;20(2):173-86. PDF

Spatiotemporally distinct PKD activation in adult cardiomyocytes in response to phenylephrine and endothelin.
Bossuyt J, Chang CW, Helmstadter K, Kunkel MT, Newton AC, Campbell KS, Martin JL, Bossuyt S, Robia SL, Bers DM.
J Biol Chem. 2011 Sep 23;286(38):33390-400. PDF

Active site inhibitors protect protein kinase C from dephosphorylation and stabilize its mature form.
Gould CM, Antal CE, Reyes G, Kunkel MT, Adams RA, Ziyar A, Riveros T, Newton AC.
J Biol Chem. 2011 Aug 19;286(33):28922-30. PDF

Hydrophobic motif phosphorylation is not required for activation loop phosphorylation of
p70 ribosomal protein S6 kinase 1 (S6K1).
Keshwani MM, von Daake S, Newton AC, Harris TK, Taylor SS.
J Biol Chem. 2011 Jul 1;286(26):23552-8. PDF

Cutting edge: PHLPP regulates the development, function, and molecular signaling pathways of regulatory T cells.
Patterson SJ, Han JM, Garcia R, Assi K, Gao T, O’Neill A, Newton AC, Levings MK.
J Immunol. 2011 May 15;186(10):5533-7. PDF

Mislocalization of the E3 ligase, beta-transducin repeat containing protein 1 (β-TrCP1)
in glioblastoma uncouples negative feedback between the PH domain
Leucine-rich repeat Protein Phosphatase 1 (PHLPP1) and Akt.
Warfel NA, Niederst M, Stevens MW, Brennan PM, Frame MC, Newton AC
J Biol Chem. 2011 Jun 3;286(22):19777-88. PDF

Spinal phosphinositide 3-kinase-Akt-mammalian target of rapamycin signaling cascades in inflammation-induced hyperalgesia.
Xu Q, Fitzsimmons B, Steinauer J, O’Neill A, Newton AC, Hua XY, Yaksh TL.
J Neurosci. 2011 Feb 9;31(6):2113-24. PDF

Regulation of Conventional and Novel Protein Kinase C Isozymes by Phosphorylation and Lipids
Newton AC
In Protein Kinase C in Cancer Signaling and Therapy,
Current Cancer Research (Springer) 2010:9-23. PDF

Protein kinase C δ-specific activity reporter reveals agonist-evoked nuclear activity controlled by Src family of kinases.
Kajimoto T, Sawamura S, Tohyama Y, Mori U, and Newton AC.
J Biol Chem. 2010 Dec 31;285(53):41896-910. PDF

Discovery of Small Molecule Inhibitors of the PH Domain Leucine-Rich Repeat Protein
Phosphatase (PHLPP) by Chemical and Virtual Screening.
Sierecki E, Sinko W, McCammon JA, Newton AC.
J Med Chem. 2010 Oct 14;53(19):6899-911. PDF

PHLPP-1 Negatively Regulates Akt Activity and Survival in the Heart.
Miyamoto S, Purcell NH, Smith JM, Gao T, Whittaker R, Huang K, Castillo
R, Glembotski CC, Sussman MA, Newton AC, Heller Brown J
Circ Res. 2010 Aug 20;107(4):476-84. PDF

Calcium transduces plasma membrane receptor signals to produce diacylglycerol at Golgi membranes.
Kunkel MT, Newton AC
J Biol Chem. 2010 Jul 23;285(30):22748–52. PDF

Interaction with AKAP79 Modifies the Cellular Pharmacology of PKC.
Hoshi N, Langeberg LK, Gould CM, Newton AC, Scott JD
Mol Cell. 2010 Feb 26;37(4):541-550. PDF

Protein kinase C: poised to signal.
Newton AC
Am J Physiol Endocrinol Metab. 2010;298:E395–E402. PDF

Protein phosphatase PHLPP1 controls the light-induced resetting of the circadian clock.
Masubuchi S, Gao T, O’Neill A, Eckel-Mahan K, Newton AC and Sassone-Corsi P
Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1642-7. PDF

Spatiotemporal Dynamics of Kinase Signaling Visualized by Targeted Reporters.
Kunkel MT, Newton AC
Curr. Protoc. Chem Biol. 2009;1:17-28. PDF

Relaying Signals from Lipid Hydrolysis to Protein Phosphorylation.
Newton AC
In Handbook of Cell Signaling (Academic Press) 2009:1123-1130.

PHLPP: PH Domain Leucine-Rich Repeat Protein Phosphatase.
Newton AC
In Handbook of Cell Signaling (Academic Press) 2009:843-848.

The protein scaffold NHERF-1 controls the amplitude and duration of localized protein kinase D activity.
Kunkel MT, Garcia EL, Kajimoto T, Hall RA, Newton AC
J Biol Chem. 2009 Sep 4;284(36):24653–61. PDF

Lipid activation of protein kinases.
Newton AC.
J Lipid Res. 2009 April Supplement:S266-S271. PDF

Common Polymorphism in the Phosphatase PHLPP2 Results in Reduced Regulation of Akt and Protein Kinase C.
Brognard J, Niederst M, Reyes G, Warfel N, Newton AC
J Biol Chem. 2009 May 29;284(22):15215-23. PDF

The chaperones Hsp90 and Cdc37 mediate the maturation and stabilization of protein kinase C
through a conserved PXXP motif in the C-terminal tail.
Gould CM, Kannan N, Taylor SS, Newton AC.
J Biol Chem. 2009 Feb 20;284(8):4921-35. PDF

AKAP-Lbc mobilizes a cardiac hypertrophy signaling pathway.
Carnegie GK, Soughayer J, Smith FD, Pedroja BS, Zhang F, Diviani D,
Bristow MR, Kunkel MT, Newton AC, Langeberg LK, Scott JD.
Mol Cell. 2008 Oct 24;32(2):169-79. PDF

Spatiotemporal dynamics of lipid signaling: Protein kinase C as a paradigm.
Gallegos LL, Newton AC.
IUBMB Life. 2008 Aug 20.

The Life and Death of Protein Kinase C.
Gould, CM, Newton AC.
Curr Drug Targets. 2008 Aug;9(8):614-25. publisher’s site

My Favorite Enzyme: Protein kinase C.
Newton AC.
IUBMB Life. 2008 Nov;60(11):765-8. PDF

The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C.
Facchinetti V, Ouyang W, Wei H, Soto N, Lazorchak A, Gould C, Lowry C,
Newton AC, Mao Y, Miao RQ, Sessa WC, Qin J, Zhang P, Su B, Jacinto E.
EMBO J. 2008 Jul 23;27(14):1932-43. PDF

PHLPPing the switch on Akt and protein kinase C signaling.
Brognard J, Newton AC.
Trends Endocrinol Metab. 2008 Aug;19(6):223-30. PDF

Kinetic Analysis of the Interaction of the C1 Domain of Protein Kinase C with Lipid Membranes by Stopped-flow Spectroscopy.
Dries DR, Newton AC.
J Biol Chem. 2008 Mar 21;283(12):7885-93. PDF

The phosphatase PHLPP controls the cellular levels of protein kinase C.
Gao T, Brognard J, Newton AC.
J Biol Chem. 2008 Mar 7;283(10):6300-6311. PDF

Induced Fit and Wit: Celebrating the Life of Daniel E. Koshland, Jr. (1920 – 2007).
Newton AC, Mochly-Rosen D.
IUBMB Life. 2007 Dec;59(12):741-3. PDF

Amplitude control of protein kinase C by RINCK, a novel E3 ubiquitin ligase.
Chen D, Gould C, Garza R, Gao T, Hampton RY, Newton AC.
J Biol Chem. 2007 Nov 16;282(46):33776-87. PDF

PHLPP and a Second Isoform, PHLPP2, Differentially Attenuate the Amplitude of
Akt Signaling by Regulating Distinct Akt Isoforms.
Brognard J, Sierecki E, Gao T, Newton AC.
Mol Cell. 2007 Mar 23;25(6):917-31. PDF

Calcium-dependent regulation of protein kinase D revealed by a genetically-encoded kinase activity reporter.
Kunkel MT, Toker A, Tsien RY, Newton AC.
J Biol Chem. 2007 Mar 2;282(9):6733-42. PDF

A single residue in the C1 domain sensitizes novel protein kinase C isoforms to cellular diacylglycerol production.
Dries DR, Gallegos LL, Newton AC.
J. Biol. Chem. 2007 Jan 12; 282(2) 826-830. PDF

Invariant Leu preceding turn phosphorylation motif controls the interaction of protein kinase C with Hsp70.
Gao T, Newton AC.
J Biol Chem. 2006 Oct 27;281(43):32461-8. PDF

Targeting protein kinase C activity reporter to discrete intracellular regions
reveals spatiotemporal differences in agonist-dependent signaling.
Gallegos LL, Kunkel MT, Newton AC.
J Biol Chem. 2006 Oct 13;281(41):30947-30956. PDF

Increased membrane affinity of the C1 domain of protein kinase Cdelta compensates
for the lack of involvement of its C2 domain in membrane recruitment.
Giorgione JR, Lin JH, McCammon JA, Newton AC.
J Biol Chem. 2006 Jan 20;281(3):1660-9. PDF

PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth.
Gao T, Furnari F, Newton AC.
Mol Cell. 2005 Apr 1;18(1):13-24. PDF

Spatio-temporal dynamics of protein kinase B/Akt signaling revealed by a genetically encoded fluorescent reporter.
Kunkel MT, Ni Q, Tsien RY, Zhang J, Newton AC.
J Biol Chem. 2005 Feb 18;280(7):5581-7. PDF

Protein Kinase C Family.
Newton AC
Encyclopedia of Biological Chemistry, 2004,3;523-526.

The adaptor protein Grb14 regulates the localization of 3-phosphoinositide-dependent kinase-1.
King CC, Newton AC.
J Biol Chem. 2004 Sep 3;279(36):37518-27. PDF

Diacylglycerol’s affair with protein kinase C turns 25.
Newton AC.
Trends Pharmacol Sci. 2004 Apr;25(4):175-7.

Centrosomal anchoring of protein kinase C betaII by pericentrin controls
microtubule organization, spindle function, and cytokinesis.
Chen D, Purohit A, Halilovic E, Doxsey SJ, Newton AC.
J Biol Chem. 2004 Feb 6;279(6):4829-39. PDF

Pathway illuminated: visualizing protein kinase C signaling.
Violin JD, Newton AC.
IUBMB Life. 2003 Dec;55(12):653-60.

Contribution of the C1A and C1B domains to the membrane interaction of protein kinase C.
Giorgione J, Hysell M, Harvey DF, Newton AC.
Biochemistry. 2003 Sep 30;42(38):11194-202. PDF

A Ras activation pathway dependent on Syk phosphorylation of protein kinase C.
Kawakami Y, Kitaura J, Yao L, McHenry RW, Kawakami Y, Newton AC, Kang S, Kato RM, Leitges M, Rawlings DJ, Kawakami T.
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9470-5. PDF

Use of stopped-flow fluorescence spectroscopy to measure rapid membrane binding by protein kinase C.
Nalefski EA, Newton AC.
Methods Mol Biol. 2003;233:115-28.

Measuring the binding of protein kinase C to sucrose-loaded vesicles.
Giorgione J, Newton AC.
Methods Mol Biol. 2003;233:105-13.

Measuring the interaction of protein kinase C with membranes: an introduction.
Newton AC.
Methods Mol Biol. 2003;233:89-92.

The ins and outs of protein kinase C.
Newton AC.
Methods Mol Biol. 2003;233:3-7.

Protein kinase C translocation by modified phorbol esters with functionalized lipophilic regions.
Bertolini TM, Giorgione J, Harvey DF, Newton AC.
J Org Chem. 2003 Jun 27;68(13):5028-36. PDF

Differential spatial and temporal phosphorylation of the visual
receptor, rhodopsin, at two primary phosphorylation sites in mice
exposed to light.
Adams RA, Liu X, Williams DS, Newton AC.
Biochem J. 2003 Sep 1;374(Pt 2):537-43. PDF

A genetically encoded fluorescent reporter reveals oscillatory phosphorylation by protein kinase C.
Violin JD, Zhang J, Tsien RY, Newton AC.
J Cell Biol. 2003 Jun 9;161(5):899-909. PDF

Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm.
Newton AC.
Biochem J. 2003 Mar 1;370(Pt 2):361-71.

Protein Kinase C: Relaying Signals from Lipid Hydrolysis to Protein Phosphorylation.
Newton AC.
In Handbook of Cell Signaling (Elsevier Science) 2003;2:187-192.

The turn motif is a phosphorylation switch that regulates the binding of Hsp70 to protein kinase C.
Gao T, Newton AC.
J Biol Chem. 2002 Aug 30;277(35):31585-92. PDF

Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells.
Zacharias DA, Violin JD, Newton AC, Tsien RY.
Science. 2002 May 3;296(5569):913-6. PDF

Regulation of novel protein kinase C epsilon by phosphorylation.
Cenni V, Doppler H, Sonnenburg ED, Maraldi N, Newton AC, Toker A.
Biochem J. 2002 May 1;363(Pt 3):537-45. PDF

Analyzing protein kinase C activation.
Newton AC.
Methods Enzymol. 2002;345:499-506.

Protein kinase C: structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions.
Newton AC.
Chem Rev. 2001 Aug;101(8):2353-64. PDF

Membrane binding kinetics of protein kinase C betaII mediated by the C2 domain.
Nalefski EA, Newton AC.
Biochemistry. 2001 Nov 6;40(44):13216-29. PDF

PKA, PKC, and AKAP localization in and around the neuromuscular junction.
Perkins GA, Wang L, Huang LJ, Humphries K, Yao VJ, Martone M, Deerinck
TJ, Barraclough DM, Violin JD, Smith D, Newton A, Scott JD, Taylor SS,
Ellisman MH.
BMC Neurosci. 2001 Oct 23;2:17. PDF

Cellular Regulation of Protein Kinase C.
Newton AC, Toker A.
In Protein Adaptations and Signal Transduction (Elsevier Science) 2001;163-173.

The phosphoinositide-dependent kinase, PDK-1, phosphorylates conventional
protein kinase C isozymes by a mechanism that is independent of
phosphoinositide 3-kinase.
Sonnenburg ED, Gao T, Newton AC.
J Biol Chem. 2001 Nov 30;276(48):45289-97. PDF

The carboxyl terminus of protein kinase c provides a switch to regulate its
interaction with the phosphoinositide-dependent kinase, PDK-1.
Gao T, Toker A, Newton AC.
J Biol Chem. 2001 Jun 1;276(22):19588-96. PDF

Cellular signaling: pivoting around PDK-1.
Toker A, Newton AC.
Cell. 2000 Oct 13;103(2):185-8.

p21-activated kinase (PAK1) is phosphorylated and activated by 3-phosphoinositide-dependent kinase-1 (PDK1).
King CC, Gardiner EM, Zenke FT, Bohl BP, Newton AC, Hemmings BA, Bokoch GM.
J Biol Chem. 2000 Dec 29;275(52):41201-9. PDF

The C1 and C2 domains of protein kinase C are independent membrane
targeting modules, with specificity for phosphatidylserine conferred by
the C1 domain.
Johnson JE, Giorgione J, Newton AC.
Biochemistry. 2000 Sep 19;39(37):11360-9. PDF

Protein kinase C isozymes and the regulation of diverse cell responses.
Dempsey EC, Newton AC, Mochly-Rosen D, Fields AP, Reyland ME, Insel PA, Messing RO.
Am J Physiol Lung Cell Mol Physiol. 2000 Sep;279(3):L429-38. PDF

Sphingosine is a novel activator of 3-phosphoinositide-dependent kinase 1.
King CC, Zenke FT, Dawson PE, Dutil EM, Newton AC, Hemmings BA, Bokoch GM.
J Biol Chem. 2000 Jun 16;275(24):18108-13. PDF

Dual role of pseudosubstrate in the coordinated regulation of protein kinase C by phosphorylation and diacylglycerol.
Dutil EM, Newton AC.
J Biol Chem. 2000 Apr 7;275(14):10697-701. PDF

Spinal PKC activity and expression: role in tolerance produced by continuous spinal morphine infusion.
Granados-Soto V, Kalcheva I, Hua X, Newton A, Yaksh TL.
Pain. 2000 Apr;85(3):395-404. PDF

Akt/protein kinase B is regulated by autophosphorylation at the hypothetical PDK-2 site.
Toker A, Newton AC.
J Biol Chem. 2000 Mar 24;275(12):8271-4. PDF

Protein Kinase C.
Newton AC
In Principles of Molecular Regulation (Humana Press) 2000;207-220.

Mechanism of A-kinase-anchoring protein 79 (AKAP79) and protein kinase C interaction.
Faux MC, Rollins EN, Edwards AS, Langeberg LK, Newton AC, Scott JD.
Biochem J. 1999 Oct 15;343 Pt 2:443-52. PDF

The hydrophobic phosphorylation motif of conventional protein kinase C is regulated by autophosphorylation.
Behn-Krappa A, Newton AC.
Curr Biol. 1999 Jul 15;9(14):728-37. PDF

Carboxyl-terminal phosphorylation regulates the function and subcellular localization of protein kinase C betaII.
Edwards AS, Faux MC, Scott JD, Newton AC.
J Biol Chem. 1999 Mar 5;274(10):6461-8.  PDF

Regulation of conventional protein kinase C isozymes by phosphoinositide-dependent kinase 1 (PDK-1).
Dutil EM, Toker A, Newton AC.
Curr Biol. 1998 Dec 17-31;8(25):1366-75. PDF

Mechanism of the apparent cooperativity in the interaction of protein kinase C with phosphatidylserine.
Mosior M, Newton AC.
Biochemistry. 1998 Dec 8;37(49):17271-9. PDF

Regulation of protein kinase C zeta by PI 3-kinase and PDK-1.
Chou MM, Hou W, Johnson J, Graham LK, Lee MH, Chen CS, Newton AC, Schaffhausen BS, Toker A.
Curr Biol. 1998 Sep 24;8(19):1069-77. PDF

Protein kinase C: a paradigm for regulation of protein function by two membrane-targeting modules.
Newton AC, Johnson JE.
Biochim Biophys Acta. 1998 Aug 21;1376(2):155-72. PDF

Protected-site phosphorylation of protein kinase C in hippocampal long-term potentiation.
Sweatt JD, Atkins CM, Johnson J, English JD, Roberson ED, Chen SJ, Newton A, Klann E.
J Neurochem. 1998 Sep;71(3):1075-85. PDF

Lipid structure and not membrane structure is the major determinant in the regulation of protein kinase C by phosphatidylserine.
Johnson JE, Zimmerman ML, Daleke DL, Newton AC.
Biochemistry. 1998 Sep 1;37(35):12020-5. PDF

Regulation of the phosphorylation state of rhodopsin by dopamine.
Udovichenko IP, Newton AC, Williams DS.
J Biol Chem. 1998 Mar 27;273(13):7181-4. PDF

Regulation of protein kinase C betaII by its C2 domain.
Edwards AS, Newton AC.
Biochemistry. 1997 Dec 16;36(50):15615-23. PDF

A putative phosphatidylserine binding motif is not involved in the lipid regulation of protein kinase C.
Johnson JE, Edwards AS, Newton AC.
J Biol Chem. 1997 Dec 5;272(49):30787-92. PDF

Characterization of protein kinase C in photoreceptor outer segments.
Williams DS, Liu X, Schlamp CL, Ondek B, Jaken S, Newton AC.
J Neurochem. 1997 Oct;69(4):1693-702. PDF

Ca2+ differentially regulates conventional protein kinase Cs’ membrane interaction and activation.
Keranen LM, Newton AC.
J Biol Chem. 1997 Oct 10;272(41):25959-67. PDF

Phosphorylation
at conserved carboxyl-terminal hydrophobic motif regulates the
catalytic and regulatory domains of protein kinase C.
Edwards AS, Newton AC.
J Biol Chem. 1997 Jul 18;272(29):18382-90. PDF

Identification of protein kinase C phosphorylation sites on bovine rhodopsin.
Greene NM, Williams DS, Newton AC.
J Biol Chem. 1997 Apr 18;272(16):10341-4. PDF

Regulation of protein kinase C.
Newton AC.
Curr Opin Cell Biol. 1997 Apr;9(2):161-7. PDF

Contribution of protein kinase C to the phosphorylation of rhodopsin in intact retinas.
Udovichenko IP, Newton AC, Williams DS.
J Biol Chem. 1997 Mar 21;272(12):7952-9. PDF

Taxonomy and function of C1 protein kinase C homology domains.
Hurley JH, Newton AC, Parker PJ, Blumberg PM, Nishizuka Y.
Protein Sci. 1997 Feb;6(2):477-80. PDF

Inhibition of the insulin receptor tyrosine kinase by phosphatidic acid.
Arnold RS, Newton AC.
J Cell Biochem. 1996 Sep 15;62(4):516-28. PDF

Protein kinase C: ports of anchor in the cell.
Newton AC.
Curr Biol. 1996 Jul 1;6(7):806-9. PDF

Diacylglycerol directly stimulates the insulin receptor tyrosine kinase.
Arnold RS, Newton AC.
FEBS Lett. 1996 Feb 12;380(1-2):58-62. PDF

Calcium-independent binding to interfacial phorbol esters causes
protein kinase C to associate with membranes in the absence of acidic
lipids.
Mosior M, Newton AC.
Biochemistry. 1996 Feb 6;35(5):1612-23. PDF

Protein kinase C is regulated in vivo by three functionally distinct phosphorylations.
Keranen LM, Dutil EM, Newton AC.
Curr Biol. 1995 Dec 1;5(12):1394-1403. PDF

Protein kinase C: structure, function, and regulation.
Newton AC.
J Biol Chem. 1995 Dec 1;270(48):28495-8. PDF

Mechanism of interaction of protein kinase C with phorbol esters. Reversibility and nature of membrane association.
Mosior M, Newton AC.
J Biol Chem. 1995 Oct 27;270(43):25526-33. PDF

Protein kinase C. Seeing two domains.
Newton AC.
Curr Biol. 1995 Sep 1;5(9):973-6. PDF

Kinetics and localization of the phosphorylation of rhodopsin by protein kinase C.
Greene NM, Williams DS, Newton AC.
J Biol Chem. 1995 Mar 24;270(12):6710-7. PDF

Isozyme-specific inhibition of protein kinase C by RNA aptamers.
Conrad R, Keranen LM, Ellington AD, Newton AC.
J Biol Chem. 1994 Dec 23;269(51):32051-4. PDF

In vivo regulation of protein kinase C by trans-phosphorylation followed by autophosphorylation.
Dutil EM, Keranen LM, DePaoli-Roach AA, Newton AC.
J Biol Chem. 1994 Nov 25;269(47):29359-62. PDF

Requirement for negative charge on “activation loop” of protein kinase C.
Orr JW, Newton AC.
J Biol Chem. 1994 Nov 4;269(44):27715-8.

Protein kinase C association with the retinal cytoskeleton and phosphorylation of vimentin.
Williams DS, Park S, Schlamp CL, Newton AC.
Exp Eye Res. 1994 Jun;58(6):747-59.

Phosphatidyl-L-serine is necessary for protein kinase C’s high-affinity
interaction with diacylglycerol-containing membranes.
Newton AC, Keranen LM.
Biochemistry. 1994 May 31;33(21):6651-8.

Intrapeptide regulation of protein kinase C.
Orr JW, Newton AC.
J Biol Chem. 1994 Mar 18;269(11):8383-7.

Protein kinase C as a measure of transbilayer phosphatidylserine asymmetry.
Daleke DL, Huestis WH, Newton AC.
Anal Biochem. 1994 Feb 15;217(1):33-40.

Gene expression of the neuropeptide-processing enzyme carboxypeptidase E in rat photoreceptor cells.
Nickells RW, Schlamp CL, Newton AC, Williams DS.
J Neurochem. 1993 Nov;61(5):1891-900.

Rhodopsin is the major in situ substrate of protein kinase C in rod outer segments of photoreceptors.
Newton AC, Williams DS.
J Biol Chem. 1993 Aug 25;268(24):18181-6.

Does protein kinase C play a role in rhodopsin desensitization?
Newton AC, Williams DS.
Trends Biochem Sci. 1993 Aug;18(8):275-7.

Interaction of proteins with lipid headgroups: lessons from protein kinase C.
Newton AC.
Annu Rev Biophys Biomol Struct. 1993;22:1-25

Reversible exposure of the pseudosubstrate domain of protein kinase C by phosphatidylserine and diacylglycerol.
Orr JW, Keranen LM, Newton AC.
J Biol Chem. 1992 Aug 5;267(22):15263-6.

Interaction of protein kinase C with phosphatidylserine. 2. Specificity and regulation.
Orr JW, Newton AC.
Biochemistry. 1992 May 19;31(19):4667-73.

Interaction of protein kinase C with phosphatidylserine. 1. Cooperativity in lipid binding.
Orr JW, Newton AC.
Biochemistry. 1992 May 19;31(19):4661-7.

Involvement of protein kinase C in the phosphorylation of rhodopsin.
Newton AC, Williams DS.
J Biol Chem. 1991 Sep 25;266(27):17725-8.

Inhibition of the insulin receptor tyrosine kinase by sphingosine.
Arnold RS, Newton AC.
Biochemistry. 1991 Aug 6;30(31):7747-54.

Phosphatidylserine affects specificity of protein kinase C substrate phosphorylation and autophosphorylation.
Newton AC, Koshland DE Jr.
Biochemistry. 1990 Jul 17;29(28):6656-61.

High cooperativity, specificity, and multiplicity in the protein kinase C-lipid interaction.
Newton AC, Koshland DE Jr.
J Biol Chem. 1989 Sep 5;264(25):14909-15.

Protein kinase C autophosphorylates by an intrapeptide reaction.
Newton AC, Koshland DE Jr.
J Biol Chem. 1987 Jul 25;262(21):10185-8.

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