Fyn Regulates Binding Partners of Cyclic-AMP Dependent Protein Kinase A
AbstractThe cAMP-dependent protein kinase A (PKA) is a serine/threonine kinase involved in many fundamental cellular processes, including migration and proliferation. Recently, we found that the Src family kinase Fyn phosphorylates the catalytic subunit of PKA (PKA-C) at Y69, thereby increasing PKA kinase activity. We also showed that Fyn induced the phosphorylation of cellular proteins within the PKA preferred target motif. This led to the hypothesis that Fyn could affect proteins in complex with PKA. To test this, we employed a quantitative mass spectrometry approach to identify Fyn-dependent binding partners in complex with PKA-C. We found Fyn enhanced the binding of PKA-C to several cytoskeletal regulators that localize to the centrosome and Golgi apparatus. Three of these Fyn-induced PKA interactors, AKAP9, PDE4DIP, and CDK5RAP2, were validated biochemically and were shown to exist in complex with Fyn and PKA in a glioblastoma cell line. Intriguingly, the complexes formed between PKA-C and these known AKAPs were dependent upon Fyn catalytic activity and expression levels. In addition, we identified Fyn-regulated phosphorylation sites on proteins in complex with PKA-C. We also identified and biochemically validated a novel PKA-C interactor, LARP4, which complexed with PKA in the absence of Fyn. These results demonstrate the ability of Fyn to influence the docking of PKA to specific cellular scaffolds and suggest that Fyn may affect the downstream substrates targeted by PKA. View Full-Text
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Schmoker, A.M.; Barritt, S.A.; Weir, M.E.; Mann, J.E.; Hogan, T.C.; Ballif, B.A.; Deming, P.B. Fyn Regulates Binding Partners of Cyclic-AMP Dependent Protein Kinase A. Proteomes 2018, 6, 37.
Schmoker AM, Barritt SA, Weir ME, Mann JE, Hogan TC, Ballif BA, Deming PB. Fyn Regulates Binding Partners of Cyclic-AMP Dependent Protein Kinase A. Proteomes. 2018; 6(4):37.Chicago/Turabian Style
Schmoker, Anna M.; Barritt, Samuel A.; Weir, Marion E.; Mann, Jacqueline E.; Hogan, Tyler C.; Ballif, Bryan A.; Deming, Paula B. 2018. "Fyn Regulates Binding Partners of Cyclic-AMP Dependent Protein Kinase A." Proteomes 6, no. 4: 37.
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