PubMed Journals: J Biol Chem
Source: PMID: 16365045
⇦ ⇨ J Biol Chem. 2006 Feb 24;281(8):4787-94.
⇩ Epub 2005 Dec 19.
The low density lipoprotein receptor-related
protein 6 interacts with glycogen synthase
kinase 3 and attenuates activity.
Mi K(1), Dolan PJ, Johnson GV.
(1) Department of Psychiatry,
University of Alabama at Birmingham,
Birmingham, Alabama 35294-0017, USA.
Glycogen synthase kinase 3 (GSK3) is a widely
expressed Ser/Thr protein kinase that phosphorylates
numerous substrates. This large number of
substrates requires precise and specific
regulation of GSK3 activity, which is achieved
by a combination of phosphorylation, localization,
and interactions with GSK3-binding proteins.
Members of the Wnt canonical pathway have
been shown to influence GSK3 activity. Through
a yeast two-hybrid screen, we identified
the Wnt canonical pathway co-receptor protein
low density lipoprotein receptor-related protein
6 (LRP6) as a GSK3-binding protein. The interaction
between the C terminus of LRP6 and GSK3 was
also confirmed by in vitro GST pull-down
assays and in situ coimmunoprecipitation
assays. In vitro assays using immunoprecipitated
proteins demonstrated that the C terminus
of LRP6 significantly attenuated the activity
of GSK3beta. In situ, LRP6 significantly
decreased GSK3beta-mediated phosphorylation
of tau at both primed and unprimed sites.
Finally, it was also demonstrated that GSK3beta
phosphorylates the PPP(S/T)P motifs in the
C terminus of LRP6. This is the first identification
of a direct interaction between LRP6 and
GSK3, which results in an attenuation of
DOI: 10.1074/jbc.M508657200 PMID: 16365045
[Indexed for MEDLINE]