PMID: 7536808May 1, 1995Paper

Phosphatase resistance of ERK2 brain kinase PK40erk2

Journal of Neurochemistry
H M RoderW Schröder

Abstract

We have previously shown that a brain protein kinase, termed PK40, catalyzes the multiple phosphorylation of the KSP-repeat site of neurofilaments (NFs) and also can transform tau proteins into the paired helical filament-like state as found in Alzheimer's disease (AD) brains. Protein sequence analysis suggests that PK40 is a form of the extracellular signal-regulated kinase ERK2. A subpopulation of ERK2 species in soluble brain fractions can be efficiently phosphorylated and activated in cell-free systems, simply by adding Mg(2+)-ATP. Two phosphoisoforms of PK40erk2 are formed in this process, which have a reduced gel mobility, very much like the ERK2 form obtained in cell culture by stimulation with growth factors. One of these low-mobility forms cannot be inactivated with protein phosphatase 2A (PP2A) or with tyrosine phosphatases. The second form can be slowly inactivated by PP2A. In this case two Ser/Thr phosphates are removed at different rates during inactivation: One phosphate is very quickly removed to result in the formation of a high-mobility 39-kDa ERK2 species without consequence for activity; the other, slowly removed Ser/Thr phosphate controls the activity but has no effect on the gel mobility of ERK2. These resu...Continue Reading

Citations

Nov 29, 1996·The Journal of Biological Chemistry·B I Giasson, W E Mushynski
Aug 26, 2011·Expert Review of Neurotherapeutics·Omer Hussain Al-Hasani, Colin Smith
Aug 26, 1998·Biochimica Et Biophysica Acta·M F Beal
May 18, 2005·Journal of the Neurological Sciences·Axel Petzold

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