Discovery - University of Dundee - Online Publications

Library & Learning Centre

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

Standard

Evolution of signal multiplexing by 14-3-3-binding 2R-ohnologue protein families in the vertebrates. / Tinti, Michele; Johnson, Catherine; Toth, Rachel; Ferrier, David E. K.; MacKintosh, Carol (Lead / Corresponding author).

In: Open Biology, Vol. 2, No. 7, 120103, 2012.

Research output: Contribution to journalArticle

Harvard

Tinti, M, Johnson, C, Toth, R, Ferrier, DEK & MacKintosh, C 2012, 'Evolution of signal multiplexing by 14-3-3-binding 2R-ohnologue protein families in the vertebrates' Open Biology, vol 2, no. 7, 120103., 10.1098/rsob.120103

APA

Tinti, M., Johnson, C., Toth, R., Ferrier, D. E. K., & MacKintosh, C. (2012). Evolution of signal multiplexing by 14-3-3-binding 2R-ohnologue protein families in the vertebrates. Open Biology, 2(7), [120103]. 10.1098/rsob.120103

Vancouver

Tinti M, Johnson C, Toth R, Ferrier DEK, MacKintosh C. Evolution of signal multiplexing by 14-3-3-binding 2R-ohnologue protein families in the vertebrates. Open Biology. 2012;2(7). 120103. Available from: 10.1098/rsob.120103

Author

Tinti, Michele; Johnson, Catherine; Toth, Rachel; Ferrier, David E. K.; MacKintosh, Carol (Lead / Corresponding author) / Evolution of signal multiplexing by 14-3-3-binding 2R-ohnologue protein families in the vertebrates.

In: Open Biology, Vol. 2, No. 7, 120103, 2012.

Research output: Contribution to journalArticle

Bibtex - Download

@article{c8b0861c7d5d4ff686bc12cbbc0dd786,
title = "Evolution of signal multiplexing by 14-3-3-binding 2R-ohnologue protein families in the vertebrates",
author = "Michele Tinti and Catherine Johnson and Rachel Toth and Ferrier, {David E. K.} and Carol MacKintosh",
year = "2012",
doi = "10.1098/rsob.120103",
volume = "2",
number = "7",
journal = "Open Biology",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Evolution of signal multiplexing by 14-3-3-binding 2R-ohnologue protein families in the vertebrates

A1 - Tinti,Michele

A1 - Johnson,Catherine

A1 - Toth,Rachel

A1 - Ferrier,David E. K.

A1 - MacKintosh,Carol

AU - Tinti,Michele

AU - Johnson,Catherine

AU - Toth,Rachel

AU - Ferrier,David E. K.

AU - MacKintosh,Carol

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

UR - http://rsob.royalsocietypublishing.org/content/2/7/120103.abstract

UR - http://www.scopus.com/inward/record.url?scp=84873901523&partnerID=8YFLogxK

U2 - 10.1098/rsob.120103

DO - 10.1098/rsob.120103

M1 - Article

JO - Open Biology

JF - Open Biology

IS - 7

VL - 2

ER -

Documents

Library & Learning Centre

Contact | Accessibility | Policy