| First Author | Deák VA | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 2 | Pages | 681-90 |
| PubMed ID | 26582204 | Mgi Jnum | J:228948 |
| Mgi Id | MGI:5749887 | Doi | 10.1074/jbc.M115.701177 |
| Citation | Deak VA, et al. (2016) The A-kinase Anchoring Protein GSKIP Regulates GSK3beta Activity and Controls Palatal Shelf Fusion in Mice. J Biol Chem 291(2):681-90 |
| abstractText | A-kinase anchoring proteins (AKAPs) represent a family of structurally diverse proteins, all of which bind PKA. A member of this family is glycogen synthase kinase 3beta (GSK3beta) interaction protein (GSKIP). GSKIP interacts with PKA and also directly interacts with GSK3beta. The physiological function of the GSKIP protein in vivo is unknown. We developed and characterized a conditional knock-out mouse model and found that GSKIP deficiency caused lethality at birth. Embryos obtained through Caesarean section at embryonic day 18.5 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 GSK3beta at Ser-9 starting early in development (embryonic day 10.5), leading to enhanced GSK3beta activity. At embryonic day 18.5, GSK3beta activity decreased to levels close to that of wild type. Our findings reveal a novel, crucial role for GSKIP in the coordination of GSK3beta signaling in palatal shelf fusion. |
