Ceramide-activated protein phosphatase-2A activity in insulin-secreting cells
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Updated: Oct 31, 2026

Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays
Published on: August 13, 2017
1Research and Medical Services, William S. Middleton Memorial VA Medical Center, Madison, WI 57305, USA. akowluru@facstaff.wisc.edu
Abstract:
Okadaic acid (OKA)-sensitive phosphatase (PP2A) activity may modulate nutrient-induced insulin secretion from pancreatic beta cells [Kowluru et al., Endocrinology 137 (1996) 2315-2323]. Ceramides, a new class of lipid second messengers may regulate PP2A [Dobrowsky and Hannun, J. Biol. Chem. (1992) 267, 5048-5051], and might play a role in cytokine-mediated apoptosis in beta cells [Sjöholm, FEBS Lett. 367 (1995) 283-286]. Therefore, we investigated the regulation of PP2A-like activity by ceramides in isolated beta (HIT-T15 or INS-1) cells. Cell-permeable (C2, C6 or C18) ceramides stimulated OKA-sensitive (but not -insensitive) phosphatase activity in a concentration-dependent manner (0-12.5 microM), with maximal stimulation (+50-100%) at < 12.5 microM. C2-dihydroceramide (a biologically inactive analog of C2 ceramide) failed to augment PP2A-like activity. Stimulatory effects of ceramides do not appear to be mediated via activation of the carboxyl methylation of the catalytic subunit of protein phosphatase 2A, since no effects of ceramides (up to 25 microM) were demonstrable on this parameter. These data identify a ceramide-activated protein phosphatase as a possible locus at which ceramides might exert their effects on beta cells leading to altered insulin secretion, and decreased cell viability followed by apoptotic cell demise.
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