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The protist, Monosiga brevicollis, has a tyrosine kinase signaling network more elaborate and diverse than found in any known metazoan
Susan L. Young,
W. Todd Miller, and
*Razavi Newman Center for Bioinformatics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037; 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.
Tyrosine kinase signaling has long been considered a hallmarkof intercellular communication, unique to multicellular animals.Our genomic analysis of the unicellular choanoflagellate Monosigabrevicollis discovers a remarkable count of 128 tyrosine kinases,38 tyrosine phosphatases, and 123 phosphotyrosine (pTyr)-bindingSH2 proteins, all higher counts than seen in any metazoan. Thiselaborate signaling network shows little orthology to metazoancounterparts yet displays many innovations reminiscent of metazoans.These include extracellular domains structurally related tothose of metazoan receptor kinases, alternative methods formembrane anchoring and phosphotyrosine interaction in cytoplasmickinases, and domain combinations that link kinases to smallGTPase signaling and transcription. These proteins also displaya wealth of combinations of known signaling domains. This uniquelydivergent and elaborate signaling network illuminates the earlyevolution of pTyr signaling, explores innovative ways to traversethe cellular signaling circuitry, and shows extensive convergentevolution, highlighting pervasive constraints on pTyr signaling.
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., andY.Z. wrote the paper.