Next Article in Journal
Early Responses to Severe Drought Stress in the Arabidopsis thaliana Cell Suspension Culture Proteome
Previous Article in Journal
Proteases Shape the Chlamydomonas Secretome: Comparison to Classical Neuropeptide Processing Machinery
Article Menu

Export Article

Open AccessFeature PaperArticle
Proteomes 2018, 6(4), 37; https://doi.org/10.3390/proteomes6040037

Fyn Regulates Binding Partners of Cyclic-AMP Dependent Protein Kinase A

1
Department of Biology, University of Vermont, Burlington, VT 05405, USA
2
Department of Biomedical and Health Sciences, University of Vermont, Burlington, VT 05405, USA
*
Authors to whom correspondence should be addressed.
These three authors contribute equally to this work.
Received: 18 July 2018 / Revised: 26 September 2018 / Accepted: 27 September 2018 / Published: 29 September 2018
Full-Text   |   PDF [4982 KB, uploaded 29 September 2018]   |  

Abstract

The 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
Keywords: protein kinase A; Fyn; AKAPs; LARP4; binding partners; mass spectrometry; SILAC; centrosome; Golgi apparatus protein kinase A; Fyn; AKAPs; LARP4; binding partners; mass spectrometry; SILAC; centrosome; Golgi apparatus
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Proteomes EISSN 2227-7382 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top