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Protein Phosphatase 1γ Isoforms Linked Interactions in the Brain

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Abstract

Posttranslational protein modifications, in particular reversible protein phosphorylation, are important regulatory mechanisms involved in cellular signaling transduction pathways. Thousands of human proteins are phosphorylatable and the tight regulation of phosphorylation states is crucial for cell maintenance and development. Protein phosphorylation occurs primarily on serine, threonine, and tyrosine residues, through the antagonistic actions of protein kinases and phosphatases. The catalytic subunit of protein phosphatase 1 (PP1), a major Ser/Thr-phosphatase, associates with a large variety of regulatory subunits that define substrate specificity and determine specific cellular pathway responses. PP1 has been shown to bind to different proteins in the brain in order to execute key and differential functions. This work reports the identification of proteins expressed in the human brain that interact with PP1γ1 and PP1γ2 isoforms by the yeast two-hybrid method. An extensive search of PP1-binding motifs was performed for the proteins identified, revealing already known PP1 regulators but also novel interactors. Moreover, our results were integrated with the data of PP1γ interacting proteins from several public web databases, permitting the development of physical maps of the novel interactions. The PP1γ interactome thus obtained allowed for the identification of novel PP1 interacting proteins, supporting novel functions of PP1γ isoforms in the human brain.

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Acknowledgments

This work was supported by the Centre for Cell Biology of the University of Aveiro, by grants from Fundação para a Ciência e Tecnologia of the Portuguese Ministry of Science and Higher Education to SLCE (SFRH/BD/41751/2007), LKG (SFRM/BD/42334/2007), SCD (SFRH/BD/21559/2005), and OBCS (POCTI/BIA-BCM/58469/2004) and from the European project to EFCS cNEUPRO (LSHM-CT-2007-037950). This paper is dedicated to the memory of Edgar F. da Cruz e Silva, the former director of the Center for Cell Biology at the University of Aveiro, who first introduced protein phosphatase interactome research in Portugal.

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No competing financial interests exist.

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Authors and Affiliations

  1. Signal Transduction Laboratory, Centre for Cell Biology, Biology Department, University of Aveiro, 3810-193, Aveiro, Portugal

    Sara L. C. Esteves, Luís Korrodi-Gregório, Cândida Z. Cotrim, Paula J. M. van Kleeff & Edgar F. da Cruz e Silva

  2. Neuroscience Laboratory, Centre for Cell Biology, Health Sciences Department, University of Aveiro, 3810-193, Aveiro, Portugal

    Sara C. Domingues & Odete A. B. da Cruz e Silva

  3. Signal Transduction Laboratory, Centre for Cell Biology, Health Sciences Department, University of Aveiro, 3810-193, Aveiro, Portugal

    Margarida Fardilha

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  1. Sara L. C. Esteves
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  2. Luís Korrodi-Gregório
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  3. Cândida Z. Cotrim
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  4. Paula J. M. van Kleeff
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  5. Sara C. Domingues
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  7. Margarida Fardilha
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  8. Edgar F. da Cruz e Silva
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Correspondence to Margarida Fardilha.

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Edgar F. da Cruz e Silva passed away on March 2, 2010.

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Esteves, S.L.C., Korrodi-Gregório, L., Cotrim, C.Z. et al. Protein Phosphatase 1γ Isoforms Linked Interactions in the Brain. J Mol Neurosci 50, 179–197 (2013). https://doi.org/10.1007/s12031-012-9902-6

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