Neurobiol Aging
Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, United States; Department of Psychiatry, New York University School of Medicine, New York, NY 10016, United States.
Published: November 2011
Cytoskeletal protein phosphorylation is frequently altered in neuropathologic states but little is known about changes during normal aging. Here we report that declining protein phosphatase activity, rather than activation of kinases, underlies aging-related neurofilament hyperphosphorylation. Purified PP2A or PP2B dephosphorylated the heavy neurofilament (NFH) subunit or its extensively phorphorylated carboxyl-terminal domain in vitro. In cultured primary hippocampal neurons, inhibiting either phosphatase induced NFH phosphorylation without activating known neurofilament kinases. Neurofilament phosphorylation in the mouse CNS, as reflected by levels of the RT-97 phosphoepitope associated with late axon maturation, more than doubled during the 12-month period after NFH expression plateaued at p21. This was accompanied by declines in levels and activity of PP2A but not PP2B, and no rise in activities of neurofilament kinases (Erk1,2, cdk5 and JNK1,2). Inhibiting PP2A in mice in vivo restored brain RT-97 to levels seen in young mice. Declining PP2A activity, therefore, can account for rising neurofilament phosphorylation in maturing brain, potentially compounding similar changes associated with adult-onset neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.neurobiolaging.2009.12.001 | DOI Listing |
Int J Mol Sci
June 2024
Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
Tumor angiogenesis, the formation of new blood vessels to support tumor growth and metastasis, is a complex process regulated by a multitude of signaling pathways. Dysregulation of signaling pathways involving protein kinases has been extensively studied, but the role of protein phosphatases in angiogenesis within the tumor microenvironment remains less explored. However, among angiogenic pathways, protein phosphatases play critical roles in modulating signaling cascades.
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The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43205, USA.
Alzheimer's disease (AD) is distinguished by the gradual loss of cognitive function, which is associated with neuronal loss and death. Accumulating evidence supports that protein phosphatases (PPs; PP1, PP2A, PP2B, PP4, PP5, PP6, and PP7) are directly linked with amyloid beta (Aβ) as well as the formation of the neurofibrillary tangles (NFTs) causing AD. Published data reported lower PP1 and PP2A activity in both gray and white matters in AD brains than in the controls, which clearly shows that dysfunctional phosphatases play a significant role in AD.
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March 2023
Renal Division, Department of Medicine, Emory University, Atlanta, GA 30322, USA.
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November 2022
Department of Biology, National Museum of Natural Science, 1 Kuan-Chien Road, Taichung 404, Taiwan. E-mail: (Gu); (Lin).
Reversible protein phosphorylation is accomplished by the opposing activities of kinases and phosphatases. We previously demonstrated the regulation of serine/threonine protein phosphatase (PP) type 2A (PP2A) and 2B (PP2B or calcineurin) during the embryonic diapause process of . In the present study, we further examine the expressions of other PPs (PP1 and PP4) during embryonic stages.
View Article and Find Full Text PDFInt J Mol Sci
December 2022
Laboratory of Signal Transduction, Institute for Biomedicine-iBiMED, Medical Sciences Department, University of Aveiro, 3810-193 Aveiro, Portugal.
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