GSK3B-interacting protein

Definition:

A-kinase anchoring protein for GSK3B and PKA that regulates or facilitates their kinase activity towards their targets. The ternary complex enhances Wnt-induced signaling by facilitating the GSK3B- and PKA-induced phosphorylation of beta-catenin leading to beta-catenin degradation and stabilization respectively. Upon cAMP activation, the ternary complex contributes to neuroprotection against oxidative stress-induced apoptosis by facilitating the PKA-induced phosphorylation of DML1 and PKA-induced inactivation of GSK3B. During neurite outgrowth promotes neuron proliferation; while increases beta-catenin-induced transcriptional activity through GSK3B kinase activity inhibition, reduces N-cadherin level to promote cell cycle progression.

References:

[1]. He-Yen Chou, et al. GSKIP is homologous to the Axin GSK3beta interaction domain and functions as a negative regulator of GSK3beta. Biochemistry. 2006 Sep 26;45(38):11379-89. [Content Brief]

[2]. Ching-Chih Lin, et al. GSKIP, an inhibitor of GSK3beta, mediates the N-cadherin/beta-catenin pool in the differentiation of SH-SY5Y cells. J Cell Biochem. 2009 Dec 15;108(6):1325-36. [Content Brief]

[3]. Joon-Khim Loh, et al. GSKIP- and GSK3-mediated anchoring strengthens cAMP/PKA/Drp1 axis signaling in the regulation of mitochondrial elongation. Biochim Biophys Acta. 2015 Aug;1853(8):1796-807. [Content Brief]

[4]. Alessandro Dema, et al. The A-Kinase Anchoring Protein (AKAP) Glycogen Synthase Kinase 3β Interaction Protein (GSKIP) Regulates β-Catenin through Its Interactions with Both Protein Kinase A (PKA) and GSK3β. J Biol Chem. 2016 Sep 9;291(37):19618-30. [Content Brief]

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