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.

			Author Information
			(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
			GSK3 activity.

			DOI: 10.1074/jbc.M508657200 PMID: 16365045
			[Indexed for MEDLINE]

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