Phosphorylation of SR proteins Sample Clauses

Phosphorylation of SR proteins is misregulation in tauopathies Glycogen synthase kinase 3 (GSK-3β) is one of the kinases that phosphorylates tau protein in vitro to an extent where its characteristics resembles PHF-tau in AD (Xxxxxx et al., 1992; Xxxxxxxxx et al., 1994). GSK-3β inhibition in rat cortical neurons causes an increase in the expression of the SR protein, SC35 in nuclear speckles, which leads to an increase in tau exon 10 inclusion (Xxxxxxxxx et al., 2004). Hence, misregulation of GSK-3β activity may alter tau exon 10 splicing through SC35 phosphorylation-dependent changes in localisation and activity, which may contribute to the aggregation of tau in NFTs observed in AD. Another kinase that phosphorylates the SR protein, ASF, is Dyrk1a kinase which has been implicated in Down’s syndrome (DS) tauopathy. There is an extra copy of chromosome 21 in DS patients as well as early onset of AD like tau pathology (Xxxxxxxxxx et al., 1985a; Xxxxxxxxxx et al., 1985b). ASF plays a very important role in promoting tau exon 10 inclusion. Dyrk1a kinase phosphorylates ASF and regulates its role in tau splicing (Xxx et al., 2008). Phosphorylation of ASF by Dyrk1a results in its localisation into nuclear speckles. This prevents ASF promotion of tau exon 10 inclusion causing an increase in tau transcripts with only three microtubule binding repeats (3R tau) and may contribute to early onset of tauopathy in DS patients (Xxx et al., 2008).