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PNAS 105 (28): 9674-9679

Copyright © 2008 by the National Academy of Sciences.

From the Cover


BIOLOGICAL SCIENCES / EVOLUTION

The protist, Monosiga brevicollis, has a tyrosine kinase signaling network more elaborate and diverse than found in any known metazoan

Gerard Manning*,{dagger}, Susan L. Young{ddagger}, W. Todd Miller§, and Yufeng Zhai*

*Razavi Newman Center for Bioinformatics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037; {ddagger}Department of Molecular and Cell Biology and Center for Integrative Genomics, University of California, Berkeley, CA 94720; and §Department of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11794

Edited by Tony Hunter, Salk Institute for Biological Studies, La Jolla, CA, and approved April 28, 2008

Received for publication February 11, 2008.

Abstract: Tyrosine kinase signaling has long been considered a hallmark of intercellular communication, unique to multicellular animals. Our genomic analysis of the unicellular choanoflagellate Monosiga brevicollis discovers a remarkable count of 128 tyrosine kinases, 38 tyrosine phosphatases, and 123 phosphotyrosine (pTyr)-binding SH2 proteins, all higher counts than seen in any metazoan. This elaborate signaling network shows little orthology to metazoan counterparts yet displays many innovations reminiscent of metazoans. These include extracellular domains structurally related to those of metazoan receptor kinases, alternative methods for membrane anchoring and phosphotyrosine interaction in cytoplasmic kinases, and domain combinations that link kinases to small GTPase signaling and transcription. These proteins also display a wealth of combinations of known signaling domains. This uniquely divergent and elaborate signaling network illuminates the early evolution of pTyr signaling, explores innovative ways to traverse the cellular signaling circuitry, and shows extensive convergent evolution, highlighting pervasive constraints on pTyr signaling.

Key Words: choanoflagellate • evolution • genome • kinome • phosphotyrosine


Freely available online through the PNAS open access option.

Author contributions: G.M., S.L.Y., and W.T.M. designed research; G.M., S.L.Y., W.T.M., and Y.Z. performed research; G.M., W.T.M., and Y.Z. contributed new reagents/analytic tools; G.M., S.L.Y., W.T.M., and Y.Z. analyzed data; and G.M., S.L.Y., W.T.M., and Y.Z. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

Data deposition: The sequences reported in this paper have been deposited in the kinase.com datbase, http://kinase.com/kinbase/FastaFiles (accession nos. Mbre0001Mbre0128).

See Commentary on page 9453.

This article contains supporting information online at www.pnas.org/cgi/content/full/0801314105/DCSupplemental.

{dagger}To whom correspondence should be addressed. E-mail: manning{at}salk.edu

© 2008 by The National Academy of Sciences of the USA


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