Specific processing of native and phosphorylated tau protein by proteases

Biochemical and Biophysical Research Communications
X WangJ M Wu

Abstract

Protein tau is a group of developmentally regulated proteins with implications in the pathogenesis of Alzheimer's disease (AD). To study whether phosphorylation of tau by different protein kinases may affect subsequent reactivity to proteases, human recombinant tau-3 was phosphorylated with PKA or a double-stranded DNA-dependent protein kinase (referred to as DNA-PK), followed by incubation with thrombin or a double-stranded DNA (dsDNA)-stimulated protease. Quantitative degradation of tau was measured by the disappearance of the substrates or the appearance of products on SDS-PAGE. With thrombin, tau-3 phosphorylated by DNA-PK was degraded faster than the native protein which was processed at a faster rate than tau-3 phosphorylated by PKA. With the dsDNA-stimulated protease, however, tau-3 phosphorylated by PKA was processed faster than that phosphorylated by DNA-PK. Thrombin-mediated degradation of DNA-PK phosphorylated tau-3 gave a pattern different from that using the native or the PKA phosphorylated tau-3 as substrates. These results suggest that the rate and/or sequence of phosphorylation at specific sites of tau may provide "micro-environments" and/or conformations which alter their accessibility and/or reactivity to prot...Continue Reading

Citations

Apr 8, 2017·Acta Neuropathologica·Tong GuoDiane P Hanger
Nov 16, 2004·The Journal of Biological Chemistry·Tetsuaki AraiPatrick L McGeer
Oct 19, 2016·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Mansi R KhannaKurt R Brunden
Dec 11, 2002·The Journal of Peptide Research : Official Journal of the American Peptide Society·M P CobaC Peña
Nov 15, 1996·The Journal of Biological Chemistry·C S ArnoldG W Hart
Jul 28, 2010·Biochemical Society Transactions·Diane P Hanger, Selina Wray

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a neurodegenerative disease. This feed focuses on the underlying role of tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's disease.