Developmental and light regulation of tumor suppressor protein PP2A in the retina
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// Ammaji Rajala 1,4 , Yuhong Wang 1,4 , Steven F. Abcouwer 5,6 , Thomas W. Gardner 5,6 and Raju V.S. Rajala 1,2,3,4 1 Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA 2 Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA 3 Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA 4 Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA 5 Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, Michigan, USA 6 W.K. Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, Michigan, USA Correspondence to: Raju V.S. Rajala, email: // Keywords : anti-oncogene; protein phosphatase-2A; mechanistic target of rapamycin; retina; protein kinase C; Gerotarget Received : October 27, 2017 Accepted : November 28, 2017 Published : December 17, 2017 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 PKCα 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.
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In the E64G Aα knockin model, phosphorylation of PP2A substrates PKCα and mTOR is enhanced, and this effect can also be induced under light-adapted conditions.
“Nevertheless, an enhanced phosphorylation of PP2A substrates PKCα and mTOR was observed, an effect that could also be induced under light-adapted conditions [94].”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [94]
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Physiologic functions of PP2A: Lessons from genetically modified mice
Reynhout, S., & Janssens, V. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.07.010 · Cited by 124 · see citing works
- Authors
- Rajala, A., Wang, Y., Abcouwer, S. F., Gardner, T. W., & Rajala, R. V. S.
- Affiliations
- Dean McGee Eye Institute (US)
- University of Michigan (US)
- Corresponding author
- Rajala, Raju V.S.
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2017-12-17
- Volume
- 9
- Issue
- 2
- Pages
- 1505-1523
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC5788578
- OpenAlex
- W2772876962
- Cited by
- 7
- References
- 47
- Citations by year
- 2022: 2 · 2020: 3 · 2019: 1 · 2018: 1
- FWCI
- 0.56
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Research to Prevent Blindness
- University of Oklahoma
- National Institutes of Health (EY12190)
- University of Oklahoma Health Sciences Center
- National Eye Institute (EY-016507, P30EY012190, EY-12190, R01EY000871, R01EY016507, R01EY020582)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK020572)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- protein phosphatase 2A, retina, retinal development, light regulation, rhodopsin, protein kinase C alpha, mTOR, protein dephosphorylation, photoreceptors, retinal neurons, tumor suppressor, inner retina, retinal degeneration, retinal pigment epithelium, retinal ganglion cells
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