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Rajala A, Wang Y, Abcouwer SF, et al. Developmental and light regulation of tumor suppressor protein PP2A in the retina. Oncotarget. 2017;9(2):1505-1523doi: 10.18632/oncotarget.23351.
Rajala, A., Wang, Y., Abcouwer, S. F., Gardner, T. W., & Rajala, R. V. S. (2018). Developmental and light regulation of tumor suppressor protein PP2A in the retina. Oncotarget, 9(2), 1505-1523. https://doi.org/10.18632/oncotarget.23351
Rajala, Ammaji, et al. "Developmental and light regulation of tumor suppressor protein PP2A in the retina." Oncotarget vol. 9,2 (2018): 1505-1523. doi: https://doi.org/10.18632/oncotarget.23351
Rajala A, Wang Y, Abcouwer SF, Gardner TW, Rajala RVS. Developmental and light regulation of tumor suppressor protein PP2A in the retina. Oncotarget. 2017 Dec 17;9(2):1505-1523. doi: 10.18632/oncotarget.23351. eCollection 2018 Jan 05. PMID: 29416710; PMCID: PMC5788578.
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Oncotarget. 2017 Dec 17;9(2):1505-1523. doi: 10.18632/oncotarget.23351. eCollection 2018 Jan 05.

Developmental and light regulation of tumor suppressor protein PP2A in the retina.

Oncotarget

Ammaji Rajala, Yuhong Wang, Steven F Abcouwer, Thomas W Gardner, Raju V S Rajala

Affiliations

  1. Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
  2. Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
  3. Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, Michigan, USA.
  4. W.K. Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, Michigan, USA.
  5. Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
  6. Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.

PMID: 29416710 PMCID: PMC5788578 DOI: 10.18632/oncotarget.23351

Abstract

Protein phosphatases are a group of universal enzymes that are responsible for the dephosphorylation of various proteins and enzymes in cells. Cellular signal transduction events are largely governed by the phosphorylation of key proteins. The length of cellular response depends on the activation of protein phosphatase that dephosphorylates the phosphate groups to halt a biological response, and fine-tune the defined cellular outcome. Dysregulation of these phosphatase(s) results in various disease phenotypes. The retina is a post-mitotic tissue, and oncogenic tyrosine and serine/ threonine kinase activities are important for retinal neuron survival. Aberrant activation of protein phosphatase(s) may have a negative effect on retinal neurons. In the current study, we characterized tumor suppressor protein phosphatase 2 (PP2A), a major serine/ threonine kinase with a broad substrate specificity. Our data suggest that PP2A is developmentally regulated in the retina, localized predominantly in the inner retina, and expressed in photoreceptor inner segments. Our findings indicate that PKCĪ± and mTOR may serve as PP2A substrates. We found that light regulates PP2A activity. Our studies also suggest that rhodopsin regulates PP2A and its substrate(s) dephosphorylation. PP2A substrate phosphorylation is increased in mice lacking the A-subunit of PP2A. However, there is no accompanying effect on retina structure and function. Together, our findings suggest that controlling the activity of PP2A in the retina may be neuroprotective.

Keywords: Gerotarget; anti-oncogene; mechanistic target of rapamycin; protein kinase C; protein phosphatase-2A; retina

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no competing financial interests.

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