In a screen for receptor protein-tyrosine kinase (RTK) genes expressed during gametogenesis in the cnidarian Hydra vulgaris, we isolated a cDNA encoding Lemon, an RTK with unusual features. Lemon is orthologous to Drosophila Dtrk, chicken Klg, and human colon carcinoma kinase-4. These genes constitute an RTK class characterized by a conserved transmembrane sequence, the presence of extracellular immunoglobulin-like repeats, and the absence of the DFG motif in the kinase domain. We provide evidence that Lemon is a component of an unusual RTK signal transduction mechanism that may involve transmembrane domain-mediated interactions and may not be dependent on its own catalytic activity. Lemon transcription is dynamically regulated in interstitial cells during asexual budding and gametogenesis. Transcriptional up-regulation occurs early in spermatogenesis and oogenesis concurrent with the local accumulation of interstitial cells in the body column of sexual polyps. (C) 2000 Academic Press.