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The A-kinase anchoring protein GSKIP regulates GSK3β activity and controls palatal shelf fusion in mice

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Item Type:Article
Title:The A-kinase anchoring protein GSKIP regulates GSK3β activity and controls palatal shelf fusion in mice
Creators Name:Deák, V.A. and Skroblin, P. and Dittmayer, C. and Knobeloch, K.P. and Bachmann, S. and Klussmann, E.
Abstract:A-kinase anchoring proteins (AKAPs) represent a family of structurally diverse proteins, all of which bind protein kinase A (PKA). A member of this family is Glycogen synthase kinase 3{beta} (GSK3{beta}) interaction protein (GSKIP). GSKIP interacts with PKA and also directly with GSK3{beta}. The physiological function of the GSKIP protein in vivo is unknown. We developed and characterized a conditional knockout mouse model and found that GSKIP deficiency caused lethality at birth. Embryos obtained through Caesarean section at embryonic day E18.5 were cyanotic, suffered from respiratory distress, and failed to initiate breathing properly. Additionally, all GSKIP-deficient embryos showed an incomplete closure of the palatal shelves accompanied by a delay in ossification along the fusion area of secondary palatal bones. On the molecular level, GSKIP deficiency resulted in decreased phosphorylation of GSK3{beta} at Ser9 starting early in development (E 10.5), leading to enhanced GSK3{beta} activity. At embryonic day 18.5 GSK3{beta} activity decreased to levels close to that of wild type. Our findings reveal a novel, crucial role for GSKIP in the coordination of GSK3{beta} signaling in palatal shelf fusion.
Keywords:A-Kinase Anchoring Protein (AKAP), Animal Model, Cell Signaling, Cyclic AMP (cAMP), Development, Glycogen Synthase Kinase 3 (GSK-3), Protein Kinase A (PKA), Animals, Mice
Source:Journal of Biological Chemistry
Publisher:American Society for Biochemistry and Molecular Biology
Page Range:681-690
Date:8 January 2016
Official Publication:https://doi.org/10.1074/jbc.M115.701177
PubMed:View item in PubMed

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