Anton Bennett, PhD
Research & Publications
Biography
News
Research Summary
Protein tyrosine phosphorylation mediates numerous fundamental physiological events such as mitogenesis, differentiation, cell movement and apoptosis. Our laboratory is interested in how protein tyrosine phosphatases (PTPs) participate in the regulation of these cellular processes. In order to decipher how PTPs regulate mammalian cell signaling we use a broad range of approaches from molecular biology to mouse genetic strategies.
The ultimate goal of our research on protein tyrosine phosphatases is to establish whether the PTPs participate in disease processes such as cancer, cardiovascular disease, diabetes and rare diseases such as muscular dystrophy. Our long-term research goals are to identify novel mechanisms of PTP regulation in disease and to leverage this information to determine whether inhibiting these enzymes might serve as novel therapeutic targets for the treatment of human diseases.
For further information please visit the Bennett Lab website - Home | Bennett Lab (bennett-lab.org)
Extensive Research Description
Cell proliferation, cell differentiation and death are controlled by signaling pathways that are mediated by protein tyrosyl phosphorylation. The net cellular level of protein tyrosyl phosphorylation is regulated by the intrinsic and opposing activities of protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Dysregulation of the net level of tyrosyl phosphorylation causes cancer, diabetes, cardiovascular disease and developmental abnormalities.
We focus our studies on how PTPs regulate cell signaling by controlling protein tyrosyl dephosphorylation. We are also exploring how PTPs participate in the pathogenesis of diseases such as obesity and diabetes, cardiovascular disease and developmental abnormalities. These research efforts are being accomplished by using integrated approaches that encompass cell biology, genetics, protein biochemistry, cell imaging and animal models. Our long-term research goals are to uncover the function of PTPs in order to identify whether these enzymes might serve as novel therapeutic targets for the treatment of human diseases.
For further information please visit the Bennett Lab website - Home | Bennett Lab (bennett-lab.org)
Coauthors
Research Interests
Cardiovascular Diseases; Musculoskeletal Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurosciences; Nutritional and Metabolic Diseases; Signal Transduction
Selected Publications
- Teaching an old dog new tricks: A new tool for protein tyrosine phosphatase substrate discoveryBennett A. Teaching an old dog new tricks: A new tool for protein tyrosine phosphatase substrate discovery. Journal Of Biological Chemistry 2023, 299: 104731. PMID: 37080392, PMCID: PMC10193000, DOI: 10.1016/j.jbc.2023.104731.
- SH2 Domain-Containing Phosphatase-SHP2 Attenuates Fibrotic Responses through Negative Regulation of Mitochondrial Metabolism in Lung FibroblastsKarampitsakos T, Galaris A, Barbayianni I, DeIuliis G, Ahangari F, Sampsonas F, Sotiropoulou V, Aidinis V, Bennett A, Herazo-Maya J, Xylourgidis N, Bakakos P, Bouros D, Kaminski N, Tzouvelekis A. SH2 Domain-Containing Phosphatase-SHP2 Attenuates Fibrotic Responses through Negative Regulation of Mitochondrial Metabolism in Lung Fibroblasts. Diagnostics 2023, 13: 1166. PMID: 36980473, PMCID: PMC10047203, DOI: 10.3390/diagnostics13061166.
- Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable?Shillingford S, Bennett A. Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable? The Annual Review Of Pharmacology And Toxicology 2023, 63: 617-636. PMID: 36662585, PMCID: PMC10127142, DOI: 10.1146/annurev-pharmtox-051921-121923.
- A novel site on dual-specificity phosphatase MKP7/DUSP16 is required for catalysis and MAPK bindingShillingford S, Zhang L, Surovtseva Y, Dorry S, Lolis E, Bennett AM. A novel site on dual-specificity phosphatase MKP7/DUSP16 is required for catalysis and MAPK binding. Journal Of Biological Chemistry 2022, 298: 102617. PMID: 36272649, PMCID: PMC9676401, DOI: 10.1016/j.jbc.2022.102617.
- Defining the structure-activity relationship for a novel class of allosteric MKP5 inhibitorsGannam Z, Jamali H, Kweon OS, Herrington J, Shillingford SR, Papini C, Gentzel E, Lolis E, Bennett AM, Ellman JA, Anderson KS. Defining the structure-activity relationship for a novel class of allosteric MKP5 inhibitors. European Journal Of Medicinal Chemistry 2022, 243: 114712. PMID: 36116232, PMCID: PMC9830533, DOI: 10.1016/j.ejmech.2022.114712.
- An Assessment of the Therapeutic Landscape for the Treatment of Heart Disease in the RASopathiesYi JS, Perla S, Bennett AM. An Assessment of the Therapeutic Landscape for the Treatment of Heart Disease in the RASopathies. Cardiovascular Drugs And Therapy 2022, 1-12. PMID: 35156148, DOI: 10.1007/s10557-022-07324-0.
- MAP Kinase Phosphatase-5 Deficiency Protects Against Pressure Overload-Induced Cardiac FibrosisZhong C, Min K, Zhao Z, Zhang C, Gao E, Huang Y, Zhang X, Baldini M, Roy R, Yang X, Koch WJ, Bennett AM, Yu J. MAP Kinase Phosphatase-5 Deficiency Protects Against Pressure Overload-Induced Cardiac Fibrosis. Frontiers In Immunology 2021, 12: 790511. PMID: 34992607, PMCID: PMC8724134, DOI: 10.3389/fimmu.2021.790511.
- Low-dose Dasatinib Ameliorates Hypertrophic Cardiomyopathy in Noonan Syndrome with Multiple LentiginesYi JS, Perla S, Huang Y, Mizuno K, Giordano FJ, Vinks AA, Bennett AM. Low-dose Dasatinib Ameliorates Hypertrophic Cardiomyopathy in Noonan Syndrome with Multiple Lentigines. Cardiovascular Drugs And Therapy 2021, 36: 589-604. PMID: 33689087, PMCID: PMC9270274, DOI: 10.1007/s10557-021-07169-z.
- Improving Obesity and Insulin Resistance by Targeting Skeletal Muscle MKP-1.Bennett AM, Lawan A. Improving Obesity and Insulin Resistance by Targeting Skeletal Muscle MKP-1. Journal Of Cellular Signaling 2020, 1: 160-168. PMID: 33179019, PMCID: PMC7654974, DOI: 10.33696/signaling.1.025.
- An allosteric site on MKP5 reveals a strategy for small-molecule inhibitionGannam Z, Min K, Shillingford SR, Zhang L, Herrington J, Abriola L, Gareiss PC, Pantouris G, Tzouvelekis A, Kaminski N, Zhang X, Yu J, Jamali H, Ellman JA, Lolis E, Anderson KS, Bennett AM. An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. Science Signaling 2020, 13 PMID: 32843541, PMCID: PMC7569488, DOI: 10.1126/scisignal.aba3043.
- Tyrosyl phosphorylation of PZR promotes hypertrophic cardiomyopathy in PTPN11-associated Noonan syndrome with multiple lentiginesYi JS, Perla S, Enyenihi L, Bennett AM. Tyrosyl phosphorylation of PZR promotes hypertrophic cardiomyopathy in PTPN11-associated Noonan syndrome with multiple lentigines. JCI Insight 2020, 5 PMID: 32584792, PMCID: PMC7455087, DOI: 10.1172/jci.insight.137753.
- O-GlcNAc transferase suppresses necroptosis and liver fibrosisZhang B, Li MD, Yin R, Liu Y, Yang Y, Mitchell-Richards KA, Nam JH, Li R, Wang L, Iwakiri Y, Chung D, Robert ME, Ehrlich BE, Bennett AM, Yu J, Nathanson MH, Yang X. O-GlcNAc transferase suppresses necroptosis and liver fibrosis. JCI Insight 2019, 4: e127709. PMID: 31672932, PMCID: PMC6948774, DOI: 10.1172/jci.insight.127709.
- SH2 domain-containing Phosphatase-(SHP)-2 blunts fibrotic responses through regulation of fibroblast mitochondrial metabolism and autophagyTzouvelekis A, Yu G, Ahangari F, Bennett A, Karampitsakos T, Bouros D, Bouros E, Kaminski N. SH2 domain-containing Phosphatase-(SHP)-2 blunts fibrotic responses through regulation of fibroblast mitochondrial metabolism and autophagy. 2019, pa583. DOI: 10.1183/13993003.congress-2019.pa583.
- Role of dual-specificity protein phosphatase DUSP10/MKP-5 in pulmonary fibrosisXylourgidis N, Min K, Ahangari F, Yu G, Herazo-Maya JD, Karampitsakos T, Aidinis V, Binzenhöfer L, Bouros D, Bennett AM, Kaminski N, Tzouvelekis A. Role of dual-specificity protein phosphatase DUSP10/MKP-5 in pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2019, 317: l678-l689. PMID: 31483681, PMCID: PMC6879900, DOI: 10.1152/ajplung.00264.2018.
- Noonan Syndrome-Associated SHP2 Dephosphorylates GluN2B to Regulate NMDA Receptor FunctionLevy AD, Xiao X, Shaw JE, Devi S, Katrancha SM, Bennett AM, Greer CA, Howe JR, Machida K, Koleske AJ. Noonan Syndrome-Associated SHP2 Dephosphorylates GluN2B to Regulate NMDA Receptor Function. Cell Reports 2018, 24: 1523-1535. PMID: 30089263, PMCID: PMC6234505, DOI: 10.1016/j.celrep.2018.07.006.
- DUSPs, twists and turns in the Journey to Vascular InflammationBennett AM. DUSPs, twists and turns in the Journey to Vascular Inflammation. The FEBS Journal 2018, 285: 1589-1592. PMID: 29682902, DOI: 10.1111/febs.14461.
- Mitogen-Activated Protein Kinase Regulation in Hepatic MetabolismLawan A, Bennett AM. Mitogen-Activated Protein Kinase Regulation in Hepatic Metabolism. Trends In Endocrinology And Metabolism 2017, 28: 868-878. PMID: 29128158, PMCID: PMC5774993, DOI: 10.1016/j.tem.2017.10.007.
- Loss of MKP-5 promotes myofiber survival by activating STAT3/Bcl-2 signaling during regenerative myogenesisMin K, Lawan A, Bennett AM. Loss of MKP-5 promotes myofiber survival by activating STAT3/Bcl-2 signaling during regenerative myogenesis. Skeletal Muscle 2017, 7: 21. PMID: 29047406, PMCID: PMC5648478, DOI: 10.1186/s13395-017-0137-7.
- MKP-5 Establishes Skeletal Muscle Metabolic Quiescence by Negatively Regulating MAPK-dependent Mitochondrial FunctionMin K, Bennett A. MKP-5 Establishes Skeletal Muscle Metabolic Quiescence by Negatively Regulating MAPK-dependent Mitochondrial Function. Medicine & Science In Sports & Exercise 2017, 49: 98. DOI: 10.1249/01.mss.0000517094.23230.9d.
- A Phosphoproteomic Screen Identifies a Guanine Nucleotide Exchange Factor for Rab3A Protein as a Mitogen-activated Protein (MAP) Kinase Phosphatase-5-regulated MAP Kinase Target in Interleukin 6 (IL-6) Secretion and Myogenesis*Lee H, Min K, Yi JS, Shi H, Chang W, Jackson L, Bennett AM. A Phosphoproteomic Screen Identifies a Guanine Nucleotide Exchange Factor for Rab3A Protein as a Mitogen-activated Protein (MAP) Kinase Phosphatase-5-regulated MAP Kinase Target in Interleukin 6 (IL-6) Secretion and Myogenesis*. Journal Of Biological Chemistry 2017, 292: 3581-3590. PMID: 28096466, PMCID: PMC5339744, DOI: 10.1074/jbc.m116.769208.
- Low-dose dasatinib rescues cardiac function in Noonan syndromeYi JS, Huang Y, Kwaczala AT, Kuo IY, Ehrlich BE, Campbell SG, Giordano FJ, Bennett AM. Low-dose dasatinib rescues cardiac function in Noonan syndrome. JCI Insight 2016, 1: e90220. PMID: 27942593, PMCID: PMC5135272, DOI: 10.1172/jci.insight.90220.
- Hepatic inositol 1,4,5 trisphosphate receptor type 1 mediates fatty liverFeriod CN, Oliveira AG, Guerra MT, Nguyen L, Richards KM, Jurczak MJ, Ruan H, Camporez JP, Yang X, Shulman GI, Bennett AM, Nathanson MH, Ehrlich BE. Hepatic inositol 1,4,5 trisphosphate receptor type 1 mediates fatty liver. Hepatology Communications 2016, 1: 23-35. PMID: 28966992, PMCID: PMC5613674, DOI: 10.1002/hep4.1012.
- SH2 domain-containing phosphatase-SHP-2 is a novel anti-fibrotic regulator in pulmonary fibrosisTzouvelekis A, Yu G, Herazo-Maya J, Woolard T, Zhang Y, Lee H, Lee P, Herzog E, Bennett A, Kaminski N. SH2 domain-containing phosphatase-SHP-2 is a novel anti-fibrotic regulator in pulmonary fibrosis. 2016, oa4979. DOI: 10.1183/13993003.congress-2016.oa4979.
- Mining the function of protein tyrosine phosphatases in health and diseaseLee H, Yi JS, Lawan A, Min K, Bennett AM. Mining the function of protein tyrosine phosphatases in health and disease. Seminars In Cell And Developmental Biology 2014, 37: 66-72. PMID: 25263013, PMCID: PMC4339398, DOI: 10.1016/j.semcdb.2014.09.021.
- Mitogen-Activated Protein Kinase Phosphatases in MetabolismLawan A, Bennett A. Mitogen-Activated Protein Kinase Phosphatases in Metabolism. 2013, 221-238. DOI: 10.1007/978-1-4614-7855-3_12.
- Improved regenerative myogenesis and muscular dystrophy in mice lacking Mkp5Shi H, Verma M, Zhang L, Dong C, Flavell RA, Bennett AM. Improved regenerative myogenesis and muscular dystrophy in mice lacking Mkp5. Journal Of Clinical Investigation 2013, 123: 2064-2077. PMID: 23543058, PMCID: PMC3635719, DOI: 10.1172/jci64375.
- Erratum: Corrigendum: Peroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesityDiano S, Liu Z, Jeong J, Dietrich M, Ruan H, Kim E, Suyama S, Kelly K, Gyengesi E, Arbiser J, Belsham D, Sarruf D, Schwartz M, Bennett A, Shanabrough M, Mobbs C, Yang X, Gao X, Horvath T. Erratum: Corrigendum: Peroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity. Nature Medicine 2011, 17: 1320-1320. DOI: 10.1038/nm1011-1320a.
- Loss of Mitogen-activated Protein Kinase Phosphatase-1 Protects from Hepatic Steatosis by Repression of Cell Death-inducing DNA Fragmentation Factor A (DFFA)-like Effector C (CIDEC)/Fat-specific Protein 27*Flach RJ, Qin H, Zhang L, Bennett AM. Loss of Mitogen-activated Protein Kinase Phosphatase-1 Protects from Hepatic Steatosis by Repression of Cell Death-inducing DNA Fragmentation Factor A (DFFA)-like Effector C (CIDEC)/Fat-specific Protein 27*. Journal Of Biological Chemistry 2011, 286: 22195-22202. PMID: 21521693, PMCID: PMC3121364, DOI: 10.1074/jbc.m110.210237.
- The MAP kinase phosphatase MKP-1 regulates BDNF-induced axon branchingJeanneteau F, Deinhardt K, Miyoshi G, Bennett AM, Chao MV. The MAP kinase phosphatase MKP-1 regulates BDNF-induced axon branching. Nature Neuroscience 2010, 13: 1373-1379. PMID: 20935641, PMCID: PMC2971689, DOI: 10.1038/nn.2655.
- MAPK phosphatase-1 facilitates the loss of oxidative myofibers associated with obesity in miceRoth RJ, Le AM, Zhang L, Kahn M, Samuel VT, Shulman GI, Bennett AM. MAPK phosphatase-1 facilitates the loss of oxidative myofibers associated with obesity in mice. Journal Of Clinical Investigation 2009, 119: 3817-3829. PMID: 19920356, PMCID: PMC2786792, DOI: 10.1172/jci39054.
- Mitogen-activated protein kinase phosphatase-1 (MKP-1): a critical regulator of innate immune responsesChi H, Bennett A, Flavell R. Mitogen-activated protein kinase phosphatase-1 (MKP-1): a critical regulator of innate immune responses. Journal Of Organ Dysfunction 2007, 3: 72-81. DOI: 10.1080/17471060601137415.
- Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminusChauvet V, Tian X, Husson H, Grimm D, Wang T, Hieseberger T, Igarashi P, Bennett A, Ibraghimov-Beskrovnaya O, Somlo S, Caplan M. Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. Journal Of Clinical Investigation 2005, 115: 788-788. DOI: 10.1172/jci21753c1.
- SHP-2 complex formation with the SHP-2 substrate-1 during C2C12 myogenesis.Kontaridis M, Liu X, Zhang L, Bennett A. SHP-2 complex formation with the SHP-2 substrate-1 during C2C12 myogenesis. Journal Of Cell Science 2001, 114: 2187-98. PMID: 11493654, DOI: 10.1242/jcs.114.11.2187.
- Differential Role of β1C and β1AIntegrin Cytoplasmic Variants in Modulating Focal Adhesion Kinase, Protein Kinase B/AKT, and Ras/Mitogen-activated Protein Kinase PathwaysFornaro M, Steger C, Bennett A, Wu J, Languino L. Differential Role of β1C and β1AIntegrin Cytoplasmic Variants in Modulating Focal Adhesion Kinase, Protein Kinase B/AKT, and Ras/Mitogen-activated Protein Kinase Pathways. Molecular Biology Of The Cell 2000, 11: 2235-2249. PMID: 10888665, PMCID: PMC14916, DOI: 10.1091/mbc.11.7.2235.
- Epidermal Growth Factor Receptor and the Adaptor Protein p52Shc Are Specific Substrates of T-Cell Protein Tyrosine PhosphataseTiganis T, Bennett A, Ravichandran K, Tonks N. Epidermal Growth Factor Receptor and the Adaptor Protein p52Shc Are Specific Substrates of T-Cell Protein Tyrosine Phosphatase. Molecular And Cellular Biology 1998, 18: 1622-1634. PMID: 9488479, PMCID: PMC108877, DOI: 10.1128/mcb.18.3.1622.
- Regulation of Distinct Stages of Skeletal Muscle Differentiation by Mitogen-Activated Protein KinasesBennett A, Tonks N. Regulation of Distinct Stages of Skeletal Muscle Differentiation by Mitogen-Activated Protein Kinases. Science 1997, 278: 1288-1291. PMID: 9360925, DOI: 10.1126/science.278.5341.1288.
- Multiple Requirements for SHPTP2 in Epidermal Growth Factor-Mediated Cell Cycle ProgressionBennett A, Hausdorff S, O’Reilly A, Freeman R, Neel B. Multiple Requirements for SHPTP2 in Epidermal Growth Factor-Mediated Cell Cycle Progression. Molecular And Cellular Biology 1996, 16: 1189-1202. PMID: 8622663, PMCID: PMC231101, DOI: 10.1128/mcb.16.3.1189.
- Different Signaling Roles of SHPTP2 in Insulin-induced GLUT1 Expression and GLUT4 Translocation ∗Hausdorff S, Bennett A, Neel B, Birnbaum M. Different Signaling Roles of SHPTP2 in Insulin-induced GLUT1 Expression and GLUT4 Translocation ∗. Journal Of Biological Chemistry 1995, 270: 12965-12968. PMID: 7768884, DOI: 10.1074/jbc.270.22.12965.
- Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras.Bennett A, Tang T, Sugimoto S, Walsh C, Neel B. Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras. Proceedings Of The National Academy Of Sciences Of The United States Of America 1994, 91: 7335-7339. PMID: 8041791, PMCID: PMC44394, DOI: 10.1073/pnas.91.15.7335.
- Calcium as a permissive factor but not an initiation factor in DNA synthesis induction in cultured rat hepatocytes by the peroxisome proliferator ciprofibrateBennett A, Williams G. Calcium as a permissive factor but not an initiation factor in DNA synthesis induction in cultured rat hepatocytes by the peroxisome proliferator ciprofibrate. Biochemical Pharmacology 1993, 46: 2219-2227. PMID: 8274155, DOI: 10.1016/0006-2952(93)90612-z.
- Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human platelet-derived growth factor receptor.Lechleider R, Sugimoto S, Bennett A, Kashishian A, Cooper J, Shoelson S, Walsh C, Neel B. Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human platelet-derived growth factor receptor. Journal Of Biological Chemistry 1993, 268: 21478-21481. PMID: 7691811, DOI: 10.1016/s0021-9258(20)80562-6.
- Alteration of rat liver endoplasmic reticulum Ca2+-ATPase thiol integrity by ciprofibrate, a peroxisome proliferatorBennett A, Williams G. Alteration of rat liver endoplasmic reticulum Ca2+-ATPase thiol integrity by ciprofibrate, a peroxisome proliferator. Biochemical Pharmacology 1993, 45: 2093-2098. PMID: 8512590, DOI: 10.1016/0006-2952(93)90021-n.
- Studies on the Effects of Peroxisome Proliferators as Novel Ca2+ Mobilizing Agents Using Indo-1-Loaded HepatocytesBennett A, Flint O, Williams G. Studies on the Effects of Peroxisome Proliferators as Novel Ca2+ Mobilizing Agents Using Indo-1-Loaded Hepatocytes. 1993, 143-151. DOI: 10.1007/978-1-4615-2828-9_17.
- Reduction of rat liver endoplasmic reticulum Ca2+-ATPase activity and mobilization of hepatic intracellular calcium by ciprofibrate, a peroxisome proliferatorBennett A, Williams G. Reduction of rat liver endoplasmic reticulum Ca2+-ATPase activity and mobilization of hepatic intracellular calcium by ciprofibrate, a peroxisome proliferator. Biochemical Pharmacology 1992, 43: 595-605. PMID: 1531754, DOI: 10.1016/0006-2952(92)90583-5.