Skip to content

Research at St Andrews

Evolution of signal multiplexing by 14-3-3-binding 2R-ohnologue protein families in the vertebrates

Research output: Contribution to journalArticle

DOI

Open Access permissions

Open

Author(s)

Michele Tinti, Catherine Johnson, Rachel Toth, David Ellard Keith Ferrier, Carol MacKintosh

School/Research organisations

Abstract

14-3-3 proteins regulate cellular responses to stimuli by docking onto pairs of phosphorylated residues on target proteins. The present study shows that the human 14-3-3-binding phosphoproteome is highly enriched in 2R-ohnologues, which are proteins in families of two to four members that were generated by two rounds of whole genome duplication at the origin of the vertebrates. We identify 2R-ohnologue families whose members share a ‘lynchpin’, defined as a 14-3-3-binding phosphosite that is conserved across members of a given family, and aligns with a Ser/Thr residue in pro-orthologues from the invertebrate chordates. For example, the human receptor expression enhancing protein (REEP) 1–4 family has the commonest type of lynchpin motif in current datasets, with a phosphorylatable serine in the –2 position relative to the 14-3-3-binding phosphosite. In contrast, the second 14-3-3-binding sites of REEPs 1–4 differ and are phosphorylated by different kinases, and hence the REEPs display different affinities for 14-3-3 dimers. We suggest a conceptual model for intracellular regulation involving protein families whose evolution into signal multiplexing systems was facilitated by 14-3-3 dimer binding to lynchpins, which gave freedom for other regulatory sites to evolve. While increased signalling complexity was needed for vertebrate life, these systems also generate vulnerability to genetic disorders.
Close

Details

Original languageEnglish
Article number120103
JournalOpen Biology
Volume2
DOIs
Publication statusPublished - Jul 2012

    Research areas

  • Branchiostoma, Ciona, Hereditary spastic paraplegia, RAB3GAP1, RAB3GAP2

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Space and time in Hox/ParaHox gene cluster evolution.

    Ferrier, D. E. K., 2019, Perspectives on Evolutionary Developmental Biology: Essays for Alessandro Minelli. Fusco, G. (ed.). Padova: Padova University Press, p. 245-258

    Research output: Chapter in Book/Report/Conference proceedingChapter

  2. Two more Posterior Hox genes and Hox cluster dispersal in echinoderms

    Szabó, R. & Ferrier, D. E. K., 27 Dec 2018, In : BMC Evolutionary Biology. 18, 13 p., 203.

    Research output: Contribution to journalArticle

  3. Transcriptional regulation of the Ciona Gsx gene in the neural plate

    Hudson, C., Esposito, R., Palladino, A., Staiano, L., Ferrier, D., Faure, E., Lemaire, P., Yasuo, H. & Spagnuolo, A., 21 Dec 2018, In : Developmental Biology. In press

    Research output: Contribution to journalArticle

  4. Amphioxus functional genomics and the origins of vertebrate gene regulation

    Marletaz, F., Firbas, P., Maeso, I., Tena, J., Bogdanovic, O., Perry, M., Wyatt, C., de la Calle-Mustienes, E., Bertrand, S., Burguera, D., Acemel, R., van Heeringen, S., Naranjo, S., Herrera-Ubeda, C., Skvortsova, K., Jimenez-Gancedo, S., Aldea, D., Marquez, Y., Buono, L., Kozmikova, I. & 41 othersPermanyer, J., Louis, A., Albuixech-Crespo, B., Le Petillon, Y., Leon Florian, A., Subirana, L., Balwierz, P. J., Duckett, P., Farahani, E., Aury, J. M., Mangenot, S., Wincker, P., Albalat, R., Benito-Gutierrez, E., Canestro, C., Castro, F., D'Aniello, S., Ferrier, D. E. K., Huang, S., Laudet, V., Marais, G., Pontarotti, P., Schubert, M., Seitz, H., Somorjai, I. M. L., Takahashi, T., Mirabeau, O., Xu, A., Yu, J-K., Carninci, P., Martinez-Morales, J., Crollius, H., Kozmik, Z., Weirauch, M., Garcia-Fernandez, J., Lister, R., Lenhard, B., Holland, P., Escriva, H., Gomez-Skarmeta, J. L. & Irimia, M., 21 Nov 2018, In : Nature. 564, 7734, p. 64-70 29 p.

    Research output: Contribution to journalArticle

  5. Horizons in evolutionary genomics: an interview with David Ferrier

    Ferrier, D. E. K., 1 Nov 2018, In : BMC Biology. 16, 3 p., 124.

    Research output: Contribution to journalArticle

Related by journal

  1. The effect of water temperature on routine swimming behaviour of new born guppies (Poecilia reticulata)

    Kent, M. & Ojanguren, A. F., 15 Apr 2015, In : Open Biology. 4, p. 547-552 6 p.

    Research output: Contribution to journalArticle

ID: 24998691