Brian Wadzinski
Last active: 4/25/2016

Profile

The integrated actions of both protein kinases and phosphatases govern the phosphorylation state of key intracellular proteins which are crucial for normal cellular function. Although less attention has been given to the protein serine/threonine phosphatases than to the serine/threonine kinases, it is nonetheless clear that this group of proteins plays an integral role in the control of cell growth and differentiation. Our overall research program is the study of cellular protein serine/threonine phosphatases (PPs); however, our studies have focused on PP2A-like enzymes. This family of holoenzymes has been implicated in many facets of cellular function including regulation of metabolic enzymes, cell-surface receptors, cytosolic protein kinases, and transcription factors. Moreover, PP2A itself is regulated in many ways which include association with regulatory subunits, activation or inactivation by associated proteins, and post-translational modifications. We are using multiple complementary approaches including biochemical, immunological, and molecular biology techniques to determine the structure, function, cellular localization, and regulation of PP2A-like enzymes. Particular emphasis has been placed on studying PP2A multi-protein complexes as a first step towards understanding in molecular detail the way phosphorylation/dephosphorylation reactions control cell signalling pathways. Our studies have revealed the existence of protein kinase/PP2A signaling modules as a new paradigm for the control of various intracellular signaling cascades.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Visualization of subunit interactions and ternary complexes of protein phosphatase 2A in mammalian cells. Mo ST, Chiang SJ, Lai TY, Cheng YL, Chung CE, Kuo SC, Reece KM, Chen YC, Chang NS, Wadzinski BE, Chiang CW (2014) PLoS One 9(12): e116074
    › Primary publication · 25536081 (PubMed) · PMC4275284 (PubMed Central)
  2. Greatwall-phosphorylated Endosulfine is both an inhibitor and a substrate of PP2A-B55 heterotrimers. Williams BC, Filter JJ, Blake-Hodek KA, Wadzinski BE, Fuda NJ, Shalloway D, Goldberg ML (2014) Elife : e01695
    › Primary publication · 24618897 (PubMed) · PMC3949306 (PubMed Central)
  3. Small G proteins Rac1 and Ras regulate serine/threonine protein phosphatase 5 (PP5)·extracellular signal-regulated kinase (ERK) complexes involved in the feedback regulation of Raf1. Mazalouskas MD, Godoy-Ruiz R, Weber DJ, Zimmer DB, Honkanen RE, Wadzinski BE (2014) J Biol Chem 289(7): 4219-32
    › Primary publication · 24371145 (PubMed) · PMC3924286 (PubMed Central)
  4. High glucose exposure promotes activation of protein phosphatase 2A in rodent islets and INS-1 832/13 β-cells by increasing the posttranslational carboxylmethylation of its catalytic subunit. Arora DK, Machhadieh B, Matti A, Wadzinski BE, Ramanadham S, Kowluru A (2014) Endocrinology 155(2): 380-91
    › Primary publication · 24265448 (PubMed) · PMC3891936 (PubMed Central)
  5. Protein phosphatase 2A family members (PP2A and PP6) associate with U1 snRNP and the spliceosome during pre-mRNA splicing. Kamoun M, Filali M, Murray MV, Awasthi S, Wadzinski BE (2013) Biochem Biophys Res Commun 440(2): 306-11
    › Primary publication · 24064353 (PubMed) · PMC3891829 (PubMed Central)
  6. Structural basis of protein phosphatase 2A stable latency. Jiang L, Stanevich V, Satyshur KA, Kong M, Watkins GR, Wadzinski BE, Sengupta R, Xing Y (2013) Nat Commun : 1699
    › Primary publication · 23591866 (PubMed) · PMC3644067 (PubMed Central)
  7. Essential roles of the Tap42-regulated protein phosphatase 2A (PP2A) family in wing imaginal disc development of Drosophila melanogaster. Wang N, Leung HT, Mazalouskas MD, Watkins GR, Gomez RJ, Wadzinski BE (2012) PLoS One 7(6): e38569
    › Primary publication · 22701670 (PubMed) · PMC3368869 (PubMed Central)
  8. Monoubiquitination promotes calpain cleavage of the protein phosphatase 2A (PP2A) regulatory subunit α4, altering PP2A stability and microtubule-associated protein phosphorylation. Watkins GR, Wang N, Mazalouskas MD, Gomez RJ, Guthrie CR, Kraemer BC, Schweiger S, Spiller BW, Wadzinski BE (2012) J Biol Chem 287(29): 24207-15
    › Primary publication · 22613722 (PubMed) · PMC3397847 (PubMed Central)
  9. The E3 ubiquitin ligase- and protein phosphatase 2A (PP2A)-binding domains of the Alpha4 protein are both required for Alpha4 to inhibit PP2A degradation. LeNoue-Newton M, Watkins GR, Zou P, Germane KL, McCorvey LR, Wadzinski BE, Spiller BW (2011) J Biol Chem 286(20): 17665-71
    › Primary publication · 21454489 (PubMed) · PMC3093842 (PubMed Central)
  10. Bacillus cereus phosphopentomutase is an alkaline phosphatase family member that exhibits an altered entry point into the catalytic cycle. Panosian TD, Nannemann DP, Watkins GR, Phelan VV, McDonald WH, Wadzinski BE, Bachmann BO, Iverson TM (2011) J Biol Chem 286(10): 8043-54
    › Primary publication · 21193409 (PubMed) · PMC3048691 (PubMed Central)
  11. Protein phosphatase 2A (PP2A) holoenzymes regulate death-associated protein kinase (DAPK) in ceramide-induced anoikis. Widau RC, Jin Y, Dixon SA, Wadzinski BE, Gallagher PJ (2010) J Biol Chem 285(18): 13827-38
    › Primary publication · 20220139 (PubMed) · PMC2859546 (PubMed Central)
  12. Alpha4 is a ubiquitin-binding protein that regulates protein serine/threonine phosphatase 2A ubiquitination. McConnell JL, Watkins GR, Soss SE, Franz HS, McCorvey LR, Spiller BW, Chazin WJ, Wadzinski BE (2010) Biochemistry 49(8): 1713-8
    › Primary publication · 20092282 (PubMed) · PMC2832797 (PubMed Central)
  13. The Balpha and Bdelta regulatory subunits of PP2A are necessary for assembly of the CaMKIV.PP2A signaling complex. Reece KM, Mazalouskas MD, Wadzinski BE (2009) Biochem Biophys Res Commun 386(4): 582-7
    › Primary publication · 19538941 (PubMed) · PMC2745967 (PubMed Central)
  14. Targeting protein serine/threonine phosphatases for drug development. McConnell JL, Wadzinski BE (2009) Mol Pharmacol 75(6): 1249-61
    › Primary publication · 19299564 (PubMed) · PMC2684880 (PubMed Central)
  15. The stability and transactivation potential of the mammalian MafA transcription factor are regulated by serine 65 phosphorylation. Guo S, Burnette R, Zhao L, Vanderford NL, Poitout V, Hagman DK, Henderson E, Ozcan S, Wadzinski BE, Stein R (2009) J Biol Chem 284(2): 759-65
    › Primary publication · 19004825 (PubMed) · PMC2613637 (PubMed Central)
  16. Role of protein phosphatase 2A in regulating the visual signaling in Drosophila. Wang N, Leung HT, Pak WL, Carl YT, Wadzinski BE, Shieh BH (2008) J Neurosci 28(6): 1444-51
    › Primary publication · 18256265 (PubMed) · PMC2275662 (PubMed Central)
  17. Insulin dysfunction induces in vivo tau hyperphosphorylation through distinct mechanisms. Planel E, Tatebayashi Y, Miyasaka T, Liu L, Wang L, Herman M, Yu WH, Luchsinger JA, Wadzinski B, Duff KE, Takashima A (2007) J Neurosci 27(50): 13635-48
    › Primary publication · 18077675 (PubMed)
  18. Identification of a PP2A-interacting protein that functions as a negative regulator of phosphatase activity in the ATM/ATR signaling pathway. McConnell JL, Gomez RJ, McCorvey LR, Law BK, Wadzinski BE (2007) Oncogene 26(41): 6021-30
    › Primary publication · 17384681 (PubMed)
  19. Isolation and characterization of PP2A holoenzymes containing FLAG-tagged B subunits. Adams DG, Wadzinski BE (2007) Methods Mol Biol : 101-11
    › Primary publication · 17200557 (PubMed)
  20. An automated fluorescence-based method for continuous assay of PP2A activity. Wegner AM, McConnell JL, Blakely RD, Wadzinski BE (2007) Methods Mol Biol : 61-9
    › Primary publication · 17200554 (PubMed)
  21. Death, cardiac dysfunction, and arrhythmias are increased by calmodulin kinase II in calcineurin cardiomyopathy. Khoo MS, Li J, Singh MV, Yang Y, Kannankeril P, Wu Y, Grueter CE, Guan X, Oddis CV, Zhang R, Mendes L, Ni G, Madu EC, Yang J, Bass M, Gomez RJ, Wadzinski BE, Olson EN, Colbran RJ, Anderson ME (2006) Circulation 114(13): 1352-9
    › Primary publication · 16982937 (PubMed)
  22. Inhibition of protein phosphatase 2A activity by selective electrophile alkylation damage. Codreanu SG, Adams DG, Dawson ES, Wadzinski BE, Liebler DC (2006) Biochemistry 45(33): 10020-9
    › Primary publication · 16906760 (PubMed)
  23. Localization of a nuclear serine/threonine protein phosphatase in insulin-secreting INS-1 cells: potential regulation by IL-1beta. Veluthakal R, Wadzinski BE, Kowluru A (2006) Apoptosis 11(8): 1401-11
    › Primary publication · 16830232 (PubMed)
  24. Identification and characterization of D-AKAP1 as a major adipocyte PKA and PP1 binding protein. Bridges D, MacDonald JA, Wadzinski B, Moorhead GB (2006) Biochem Biophys Res Commun 346(1): 351-7
    › Primary publication · 16756943 (PubMed)
  25. Phosphorylation of serine 526 is required for MEKK3 activity, and association with 14-3-3 blocks dephosphorylation. Fritz A, Brayer KJ, McCormick N, Adams DG, Wadzinski BE, Vaillancourt RR (2006) J Biol Chem 281(10): 6236-45
    › Primary publication · 16407301 (PubMed)
  26. Positive regulation of Raf1-MEK1/2-ERK1/2 signaling by protein serine/threonine phosphatase 2A holoenzymes. Adams DG, Coffee RL, Zhang H, Pelech S, Strack S, Wadzinski BE (2005) J Biol Chem 280(52): 42644-54
    › Primary publication · 16239230 (PubMed)
  27. Distinct protein phosphatase 2A heterotrimers modulate growth factor signaling to extracellular signal-regulated kinases and Akt. Van Kanegan MJ, Adams DG, Wadzinski BE, Strack S (2005) J Biol Chem 280(43): 36029-36
    › Primary publication · 16129692 (PubMed)
  28. Positive regulation of IkappaB kinase signaling by protein serine/threonine phosphatase 2A. Kray AE, Carter RS, Pennington KN, Gomez RJ, Sanders LE, Llanes JM, Khan WN, Ballard DW, Wadzinski BE (2005) J Biol Chem 280(43): 35974-82
    › Primary publication · 16126728 (PubMed)
  29. Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4. Zhang X, Ozawa Y, Lee H, Wen YD, Tan TH, Wadzinski BE, Seto E (2005) Genes Dev 19(7): 827-39
    › Primary publication · 15805470 (PubMed) · PMC1074320 (PubMed Central)
  30. A dynamic equilibrium between CDKs and PP2A modulates phosphorylation of pRB, p107 and p130. Garriga J, Jayaraman AL, Limón A, Jayadeva G, Sotillo E, Truongcao M, Patsialou A, Wadzinski BE, Graña X (2004) Cell Cycle 3(10): 1320-30
    › Primary publication · 15467457 (PubMed)
  31. O-GlcNAc transferase is in a functional complex with protein phosphatase 1 catalytic subunits. Wells L, Kreppel LK, Comer FI, Wadzinski BE, Hart GW (2004) J Biol Chem 279(37): 38466-70
    › Primary publication · 15247246 (PubMed)
  32. Regulation and function of the calcium/calmodulin-dependent protein kinase IV/protein serine/threonine phosphatase 2A signaling complex. Anderson KA, Noeldner PK, Reece K, Wadzinski BE, Means AR (2004) J Biol Chem 279(30): 31708-16
    › Primary publication · 15143065 (PubMed)
  33. Analysis of specific interactions of native protein phosphatase 1 isoforms with targeting subunits. Colbran RJ, Carmody LC, Bauman PA, Wadzinski BE, Bass MA (2003) Methods Enzymol : 156-75
    › Primary publication · 14674248 (PubMed)
  34. Parallel purification of three catalytic subunits of the protein serine/threonine phosphatase 2A family (PP2A(C), PP4(C), and PP6(C)) and analysis of the interaction of PP2A(C) with alpha4 protein. Kloeker S, Reed R, McConnell JL, Chang D, Tran K, Westphal RS, Law BK, Colbran RJ, Kamoun M, Campbell KS, Wadzinski BE (2003) Protein Expr Purif 31(1): 19-33
    › Primary publication · 12963337 (PubMed)
  35. A developmentally regulated, neuron-specific splice variant of the variable subunit Bbeta targets protein phosphatase 2A to mitochondria and modulates apoptosis. Dagda RK, Zaucha JA, Wadzinski BE, Strack S (2003) J Biol Chem 278(27): 24976-85
    › Primary publication · 12716901 (PubMed)
  36. Xylulose 5-phosphate mediates glucose-induced lipogenesis by xylulose 5-phosphate-activated protein phosphatase in rat liver. Kabashima T, Kawaguchi T, Wadzinski BE, Uyeda K (2003) Proc Natl Acad Sci U S A 100(9): 5107-12
    › Primary publication · 12684532 (PubMed) · PMC154306 (PubMed Central)
  37. A novel in vitro assay for deubiquitination of I kappa B alpha. Strayhorn WD, Wadzinski BE (2002) Arch Biochem Biophys 400(1): 76-84
    › Primary publication · 11913973 (PubMed)
  38. Cloning and characterization of a novel subunit of protein serine/threonine phosphatase 4 from mesangial cells. Wada T, Miyata T, Inagi R, Nangaku M, Wagatsuma M, Suzuki D, Wadzinski BE, Okubo K, Kurokawa K (2001) J Am Soc Nephrol 12(12): 2601-8
    › Primary publication · 11729228 (PubMed)
  39. Protein phosphatase 2A interacts with and directly dephosphorylates RelA. Yang J, Fan GH, Wadzinski BE, Sakurai H, Richmond A (2001) J Biol Chem 276(51): 47828-33
    › Primary publication · 11591705 (PubMed) · PMC2665282 (PubMed Central)
  40. Protein phosphatase 2A activates the proapoptotic function of BAD in interleukin- 3-dependent lymphoid cells by a mechanism requiring 14-3-3 dissociation. Chiang CW, Harris G, Ellig C, Masters SC, Subramanian R, Shenolikar S, Wadzinski BE, Yang E (2001) Blood 97(5): 1289-97
    › Primary publication · 11222372 (PubMed)
  41. Cocaine and antidepressant-sensitive biogenic amine transporters exist in regulated complexes with protein phosphatase 2A. Bauman AL, Apparsundaram S, Ramamoorthy S, Wadzinski BE, Vaughan RA, Blakely RD (2000) J Neurosci 20(20): 7571-8
    › Primary publication · 11027216 (PubMed)
  42. Reversible phosphorylation of the signal transduction complex in Drosophila photoreceptors. Liu M, Parker LL, Wadzinski BE, Shieh BH (2000) J Biol Chem 275(16): 12194-9
    › Primary publication · 10766855 (PubMed)
  43. Brain actin-associated protein phosphatase 1 holoenzymes containing spinophilin, neurabin, and selected catalytic subunit isoforms. MacMillan LB, Bass MA, Cheng N, Howard EF, Tamura M, Strack S, Wadzinski BE, Colbran RJ (1999) J Biol Chem 274(50): 35845-54
    › Primary publication · 10585469 (PubMed)
  44. An anchoring factor targets protein phosphatase 2A to brain microtubules. Price NE, Wadzinski B, Mumby MC (1999) Brain Res Mol Brain Res 73(1-2): 68-77
    › Primary publication · 10581399 (PubMed)
  45. Cloning and characterization of B delta, a novel regulatory subunit of protein phosphatase 2A. Strack S, Chang D, Zaucha JA, Colbran RJ, Wadzinski BE (1999) FEBS Lett 460(3): 462-6
    › Primary publication · 10556517 (PubMed)
  46. Differential cellular and subcellular localization of protein phosphatase 1 isoforms in brain. Strack S, Kini S, Ebner FF, Wadzinski BE, Colbran RJ (1999) J Comp Neurol 413(3): 373-84
    › Primary publication · 10502246 (PubMed)
  47. Identification of a type 6 protein ser/thr phosphatase regulated by interleukin-2 stimulation. Filali M, Li S, Kim HW, Wadzinski B, Kamoun M (1999) J Cell Biochem 73(2): 153-63
    › Primary publication · 10227379 (PubMed)
  48. Methylated C-terminal leucine residue of PP2A catalytic subunit is important for binding of regulatory Balpha subunit. Bryant JC, Westphal RS, Wadzinski BE (1999) Biochem J : 241-6
    › Primary publication · 10191253 (PubMed) · PMC1220151 (PubMed Central)
  49. Purification and identification of a novel subunit of protein serine/threonine phosphatase 4. Kloeker S, Wadzinski BE (1999) J Biol Chem 274(9): 5339-47
    › Primary publication · 10026142 (PubMed)
  50. Identification of kinase-phosphatase signaling modules composed of p70 S6 kinase-protein phosphatase 2A (PP2A) and p21-activated kinase-PP2A. Westphal RS, Coffee RL, Marotta A, Pelech SL, Wadzinski BE (1999) J Biol Chem 274(2): 687-92
    › Primary publication · 9873003 (PubMed)
  51. protein phosphatase 2A regulatory subunits. cDNA cloning and analysis of mRNA expression. Zaucha JA, Westphal RS, Wadzinski BE (1998) Methods Mol Biol : 279-91
    › Primary publication · 9664545 (PubMed)
  52. A signaling complex of Ca2+-calmodulin-dependent protein kinase IV and protein phosphatase 2A. Westphal RS, Anderson KA, Means AR, Wadzinski BE (1998) Science 280(5367): 1258-61
    › Primary publication · 9596578 (PubMed)
  53. Brain protein phosphatase 2A: developmental regulation and distinct cellular and subcellular localization by B subunits. Strack S, Zaucha JA, Ebner FF, Colbran RJ, Wadzinski BE (1998) J Comp Neurol 392(4): 515-27
    › Primary publication · 9514514 (PubMed)
  54. Protein serine/threonine phosphatase 1 and 2A associate with and dephosphorylate neurofilaments. Strack S, Westphal RS, Colbran RJ, Ebner FF, Wadzinski BE (1997) Brain Res Mol Brain Res 49(1-2): 15-28
    › Primary publication · 9387859 (PubMed)
  55. Carboxymethylation of nuclear protein serine/threonine phosphatase X. Kloeker S, Bryant JC, Strack S, Colbran RJ, Wadzinski BE (1997) Biochem J : 481-6
    › Primary publication · 9359419 (PubMed) · PMC1218819 (PubMed Central)
  56. Association of brain protein phosphatase 1 with cytoskeletal targeting/regulatory subunits. Colbran RJ, Bass MA, McNeill RB, Bollen M, Zhao S, Wadzinski BE, Strack S (1997) J Neurochem 69(3): 920-9
    › Primary publication · 9282913 (PubMed)
  57. Differential inactivation of postsynaptic density-associated and soluble Ca2+/calmodulin-dependent protein kinase II by protein phosphatases 1 and 2A. Strack S, Barban MA, Wadzinski BE, Colbran RJ (1997) J Neurochem 68(5): 2119-28
    › Primary publication · 9109540 (PubMed)
  58. Localization of the calcium/calmodulin-dependent protein phosphatase, calcineurin, in the hindbrain and spinal cord of the rat. Strack S, Wadzinski BE, Ebner FF (1996) J Comp Neurol 375(1): 66-76
    › Primary publication · 8913893 (PubMed)