Hunter T. Why nature chose phosphate to modify proteins. Philos Trans R Soc Lond B Biol Sci. 2009;367:2513–6.
Thorner J, Hunter T, Cantley LC, Sever R. Signal transduction: From the atomic age to the post-genomic era. Cold Spring Harb Perspect Biol. 2014;6:a022913.
Article PubMed PubMed Central Google Scholar
Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science. 2002;298:1912–34.
Article ADS CAS PubMed Google Scholar
Chen MJ, Dixon JE, Manning G. Genomics and evolution of protein phosphatases. Sci Signal. 2017;10:eaag1796.
Pawson T, Scott JD. Protein phosphorylation in signaling–50 years and counting. Trends Biochem Sci. 2005;30:286–90.
Article CAS PubMed Google Scholar
Lemmon MA, Freed DM, Schlessinger J, Kiyatkin A. The Dark Side of Cell Signaling: Positive Roles for Negative Regulators. Cell. 2016;164:1172–84.
Article CAS PubMed PubMed Central Google Scholar
Janssens V, Goris J. Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem J. 2001;353:417–39.
Article CAS PubMed PubMed Central Google Scholar
Reynhout S, Janssens V. Physiologic functions of PP2A: Lessons from genetically modified mice. Biochim Biophys Acta Mol Cell Res. 2019;1866:31–50.
Article CAS PubMed Google Scholar
Seshacharyulu P, Pandey P, Datta K, Batra SK. Phosphatase: PP2A structural importance, regulation and its aberrant expression in cancer. Cancer Lett. 2013;335:9–18.
Article CAS PubMed PubMed Central Google Scholar
Lambrecht C, Haesen D, Sents W, Ivanova E, Janssens V. Structure, regulation, and pharmacological modulation of PP2A phosphatases. Methods Mol Biol. 2013;1053:283–305.
Article CAS PubMed Google Scholar
Kremmer E, Ohst K, Kiefer J, Brewis N, Walter G. Separation of PP2A core enzyme and holoenzyme with monoclonal antibodies against the regulatory A subunit: abundant expression of both forms in cells. Mol Cell Biol. 1997;17:1692–701.
Article CAS PubMed PubMed Central Google Scholar
Bennin DA, Don AS, Brake T, McKenzie JL, Rosenbaum H, Ortiz L, DePaoli-Roach AA, Horne MC. Cyclin G2 associates with protein phosphatase 2A catalytic and regulatory B’ subunits in active complexes and induces nuclear aberrations and a G1/S phase cell cycle arrest. J Biol Chem. 2002;277:27449–67.
Article CAS PubMed Google Scholar
Sents W, Ivanova E, Lambrecht C, Haesen D, Janssens V. The biogenesis of active protein phosphatase 2A holoenzymes: a tightly regulated process creating phosphatase specificity. FEBS J. 2013;280:644–61.
Article CAS PubMed Google Scholar
Jiang L, Stanevich V, Satyshur KA, Kong M, Watkins GR, Wadzinski BE, Sengupta R, Xing Y. Structural basis of protein phosphatase 2A stable latency. Nat Commun. 2013;4:1699.
Article ADS PubMed Google Scholar
Cayla X, Van Hoof C, Bosch M, Waelkens E, Vandekerckhove J, Peeters B, Merlevede W, Goris J. Molecular cloning, expression, and characterization of PTPA, a protein that activates the tyrosyl phosphatase activity of protein phosphatase 2A. J Biol Chem. 1994;269:15668–75.
Article CAS PubMed Google Scholar
Van Hoof C, Goris J. PP2A fulfills its promises as tumor suppressor: which subunits are important? Cancer Cell. 2004;5:105–6.
Kauko O, Westermarck J. Non-genomic mechanisms of protein phosphatase 2A (PP2A) regulation in cancer. Int J Biochem Cell Biol. 2018;96:157–64.
Article CAS PubMed Google Scholar
Javadpour P, Dargahi L, Ahmadiani A, Ghasemi R. To be or not to be: PP2A as a dual player in CNS functions, its role in neurodegeneration, and its interaction with brain insulin signaling. Cell Mol Life Sci. 2019;76:2277–97.
Mumby M. PP2A: unveiling a reluctant tumor suppressor. Cell. 2007;130:21–4.
Article CAS PubMed Google Scholar
Kraus S, Levy G, Hanoch T, Naor Z, Seger R. Gonadotropin-releasing hormone induces apoptosis of prostate cancer cells: role of c-Jun NH2-terminal kinase, protein kinase B, and extracellular signal-regulated kinase pathways. Cancer Res. 2004;64:5736–44.
Article CAS PubMed Google Scholar
Nadel G, Yao Z, Ben-Ami I, Naor Z, Seger R. Gq-Induced Apoptosis is Mediated by AKT Inhibition That Leads to PKC-Induced JNK Activation. Cell Physiol Biochem. 2018;50:121–35.
Article CAS PubMed Google Scholar
Nadel G, Yao Z, Wainstein E, Cohen I, Ben-Ami I, Schajnovitz A, Maik-Rachline G, Naor Z, Horwitz BA, Seger R. GqPCR-stimulated dephosphorylation of AKT is induced by an IGBP1-mediated PP2A switch. Cell Commun Signal. 2022;20:5.
Article CAS PubMed PubMed Central Google Scholar
Hemmings BA. AKT Signaling: linking membrane events to life and death decision. Science. 1997;275:628–30.
Article CAS PubMed Google Scholar
Padmanabhan S, Mukhopadhyay A, Narasimhan SD, Tesz G, Czech MP, Tissenbaum HA. A PP2A regulatory subunit regulates C. elegans insulin/IGF-1 signaling by modulating AKT-1 phosphorylation. Cell. 2009;136:939–51.
Article CAS PubMed PubMed Central Google Scholar
Manning BD, Toker A. AKT/PKB Signaling: Navigating the Network. Cell. 2017;169:381–405.
Article CAS PubMed PubMed Central Google Scholar
Rodgers JT, Vogel RO, Puigserver P. Clk2 and B56beta mediate insulin-regulated assembly of the PP2A phosphatase holoenzyme complex on Akt. Mol Cell. 2011;41:471–9.
Article CAS PubMed PubMed Central Google Scholar
Ruvolo PP, Qui YH, Coombes KR, Zhang N, Ruvolo VR, Borthakur G, Konopleva M, Andreeff M, Kornblau SM. Low expression of PP2A regulatory subunit B55alpha is associated with T308 phosphorylation of AKT and shorter complete remission duration in acute myeloid leukemia patients. Leukemia. 2011;25:1711–7.
Article CAS PubMed PubMed Central Google Scholar
Shouse G, de Necochea-Campion R, Mirshahidi S, Liu X, Chen CS. Novel B55alpha-PP2A mutations in AML promote AKT T308 phosphorylation and sensitivity to AKT inhibitor-induced growth arrest. Oncotarget. 2016;7:61081–92.
Article PubMed PubMed Central Google Scholar
Levi NL, Hanoch T, Benard O, Rozenblat M, Harris D, Reiss N, Naor Z, Seger R. Stimulation of Jun N-terminal kinase (JNK) by gonadotropin-releasing hormone in pituitary alpha T3–1 cell line is mediated by protein kinase C, c-Src, and CDC42. Mol Endocrinol. 1998;12:815–24.
Chuderland D, Seger R. Calcium regulates ERK signaling by modulating its protein-protein interactions. Commun Integr Biol. 2008;1:4–5.
Article CAS PubMed PubMed Central Google Scholar
Rubinfeld H, Hanoch T, Seger R. Identification of a cytoplasmic-retention sequence in ERK2. J Biol Chem. 1999;274:30349–52.
Article CAS PubMed Google Scholar
Maik-Rachline G, Zehorai E, Hanoch T, Blenis J, Seger R. The nuclear translocation of the kinases p38 and JNK promotes inflammation-induced cancer. Sci Signal. 2018;11:eaao3428.
Procaccia S, Ordan M, Cohen I, Bendetz-Nezer S, Seger R. Direct binding of MEK1 and MEK2 to AKT induces Foxo1 phosphorylation, cellular migration and metastasis. Sci Rep. 2017;7:43078.
Article ADS CAS PubMed PubMed Central Google Scholar
Dobkin-Bekman M, Rahamin-Ben Navi L, Shterntal B, Sviridonov L, Przedecki F, Naidich-Exler M, Brodie C, Seger R, Naor Z. Differential role of PKC isoforms in GnRH and phorbol 12-myristate 13-acetate activation of extracellular signal-regulated kinase and Jun N-terminal kinase. Endocrinology. 2010;151:4894–907.
Article CAS PubMed Google Scholar
Tzivion G, Dobson M, Ramakrishnan G. FoxO transcription factors; Regulation by AKT and 14-3-3 proteins. Biochim Biophys Acta. 2011;1813:1938–45.
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