Facilitating Multicellularity

Abstract

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]