Editors' ChoicePathway Evolution

Facilitating Multicellularity

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Science Signaling  22 Jul 2008:
Vol. 1, Issue 29, pp. ec262
DOI: 10.1126/scisignal.129ec262

Tyrosine kinase (TK) signaling plays an integral role in intercellular communication in multicellular animals (metazoans). There are three molecular components essential for TK signaling: protein tyrosine kinases (PTKs), protein tyrosine phosphatases (PTPs), and SH2 domains (which mediate tyrosine phosphorylation-dependent protein-protein interactions). Once thought to be limited to metazoans, TK signaling components have also been identified in choanoflagellates, their closest unicellular relatives. Monosiga brevicollis, a colony-forming choanoflagellate, has emerged as a model in which to study the cell biological processes that correlate with the emergence of multicellularity. Manning et al. and Pincus et al. address the evolution of TK signaling. Both groups surveyed the Monosiga genome for genes that encode proteins containing PTK, PTP, and SH2 domains and report a large number, most of which have no metazoan orthologs, of each class. For example, only eight of the Monosiga TKs identified by Manning et al. have metazoan orthologs, and all of these are Src-related, which indicates that the majority of expansion and diversification of the PTP-, PTK-, and SH2-containing proteins occurred after the two lineages diverged. Both lineages have independently evolved similar repertoires of functionality through domain shuffling and convergent evolution. For example, receptor tyrosine kinases with cysteine-rich motifs have evolved in both lineages. Pincus et al. compared tyrosine kinase signaling components across 41 eukaryotes and proposed a model for the emergence of TK signaling systems. Fungi and slime molds, eukaryotes outside the metazoan-choanoflagellate lineage, have PTPs and SH2-containing proteins but not PTKs. Pincus et al. point out that even having only these two components could be advantageous because some serine-threonine kinases, which fungi and slime molds have in abundance, do perform tyrosine phosphorylation, albeit inefficiently. The authors propose that the first PTK arose from a spontaneous mutation that rendered one of the less selective serine-threonine kinases capable of phosphorylating only tyrosine residues. The number of types of PTPs, PTKs, and SH2 domains expanded in the metazoan-choanoflagellate lineage as cells exploited this new pathway to communicate with one another. Mayer provides a clear synthesis of the two studies’ combined findings.

G. Manning, S. L. Young, W. T. Miller, Y. Zhai, The protist, Monosiga brevicollis, has a tyrosine kinase signaling network more elaborate and diverse than found in any known metazoan. Proc. Natl. Acad. Sci. U.S.A. 105, 9674-9679 (2008). [Abstract] [Full Text]

D. Pincus, I. Letunic, P. Bork, W. A. Lim, Evolution of the phospho-tyrosine signaling machinery in premetazoan lineages. Proc. Natl. Acad. Sci. U.S.A. 105, 9680-9684 (2008). [Abstract] [Full Text]

B. J. Mayer, Clues to the evolution of complex signaling machinery. Proc. Natl. Acad. Sci. U.S.A. 105, 9453-9454 (2008). [Full Text]

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