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.