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Evolution of the phospho-tyrosine signaling machinery in premetazoan lineages
Peer Bork, and
Wendell A. Lim*,
*Department of Cellular and Molecular Pharmacology, University of California, 600 16th Street, San Francisco, CA 94158; and European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Communicated by Henry R. Bourne, University of California, San Francisco, CA, April 3, 2008
Received for publication February 12, 2008.
Multicellular animals use a three-part molecular toolkit tomediate phospho-tyrosine signaling: Tyrosine kinases (TyrK),protein tyrosine phosphatases (PTP), and Src Homology 2 (SH2)domains function, respectively, as "writers," "erasers," and"readers" of phospho-tyrosine modifications. How did this systemof three components evolve, given their interdependent function?Here, we examine the usage of these components in 41 eukaryoticgenomes, including the newly sequenced genome of the choanoflagellate,Monosiga brevicollis, the closest known unicellular relativeto metazoans. This analysis indicates that SH2 and PTP domainslikely evolved earliest—a handful of these domains arefound in premetazoan eukaryotes lacking tyrosine kinases, mostlikely to deal with limited tyrosine phosphorylation cross-catalyzedby promiscuous Ser/Thr kinases. Modern TyrK proteins, however,are only observed in two lineages, metazoans and choanoflagellates.These two lineages show a dramatic coexpansion of all threedomain families. Concurrent expansion of the three domain familiesis consistent with a stepwise evolutionary model in which preexistingSH2 and PTP domains were of limited utility until the appearanceof the TyrK domain in the last common ancestor of metazoansand choanoflagellates. The emergence of the full three-componentsignaling system, with its dramatically increased encoding potential,may have contributed to the advent of metazoan multicellularity.
Freely available online through the PNAS open access option.
Author contributions: P.B. and W.A.L. designed research; D.P.and I.L. performed research; I.L. and P.B. contributed new reagents/analytictools; D.P. and W.A.L. analyzed data; and D.P. and W.A.L. wrotethe paper.