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Sci. Signal., 6 December 2011
Vol. 4, Issue 202, p. ra83
[DOI: 10.1126/scisignal.2002105]

RESEARCH ARTICLES

The SH2 Domain–Containing Proteins in 21 Species Establish the Provenance and Scope of Phosphotyrosine Signaling in Eukaryotes

Bernard A. Liu1,2*, Eshana Shah1, Karl Jablonowski1, Andrew Stergachis1, Brett Engelmann1,3, and Piers D. Nash1,2{dagger}

1 Ben May Department for Cancer Research, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
2 Committee on Cancer Biology, University of Chicago, Chicago, IL 60637, USA.
3 Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.

* Present address: Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.

Abstract: The Src homology 2 (SH2) domains are participants in metazoan signal transduction, acting as primary mediators for regulated protein-protein interactions with tyrosine-phosphorylated substrates. Here, we describe the origin and evolution of SH2 domain proteins by means of sequence analysis from 21 eukaryotic organisms from the basal unicellular eukaryotes, where SH2 domains first appeared, through the multicellular animals and increasingly complex metazoans. On the basis of our results, SH2 domains and phosphotyrosine signaling emerged in the early Unikonta, and the numbers of SH2 domains expanded in the choanoflagellate and metazoan lineages with the development of tyrosine kinases, leading to rapid elaboration of phosphotyrosine signaling in early multicellular animals. Our results also indicated that SH2 domains coevolved and the number of the domains expanded alongside protein tyrosine kinases and tyrosine phosphatases, thereby coupling phosphotyrosine signaling to downstream signaling networks. Gene duplication combined with domain gain or loss produced novel SH2-containing proteins that function within phosphotyrosine signaling, which likely have contributed to diversity and complexity in metazoans. We found that intra- and intermolecular interactions within and between SH2 domain proteins increased in prevalence along with organismal complexity and may function to generate more highly connected and robust phosphotyrosine signaling networks.

{dagger} To whom correspondence should be addressed. E-mail: pdnash.uchicago{at}gmail.com

Citation: B. A. Liu, E. Shah, K. Jablonowski, A. Stergachis, B. Engelmann, P. D. Nash, The SH2 Domain–Containing Proteins in 21 Species Establish the Provenance and Scope of Phosphotyrosine Signaling in Eukaryotes. Sci. Signal. 4, ra83 (2011).

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