A partial comparison of some CAR/GSK3 and Fz/GSK3 pathways in vertebrates, Dictyostelium, and C. elegans. In all systems, 7-TM receptor signaling converges at GSK3 to regulate cell fate decisions; see text for details. In the vertebrates (and in Drosophila), Wnt/Fz signaling is antagonistic to GSK3 function. Dorsal/ventral patterning and tumorigenic fate represent only 2 examples of opposing choices determined by the presence or absence of an activated Wnt pathway. In contrast, endoderm/mesoderm formation in C. elegans is regulated by an activating Wnt/Fz signal through GSK3. In other pathways (e.g., vulval development) of C. elegans, Wnt signaling reflects the more canonical inhibitory state. Dictyostelium incorporates both activating and de-activating receptor signals through GSK3. The activating pathway requires tyrosine phosphorylation of GSK3 by ZAK1, while these tyrosines are de-phosphorylated in the CAR4-dependent inhibitory pathway. Potentially, tyrosine phosphorylation of GSK3 in C. elegans may mediate GSK3 activation via Wnt signaling. In contrast, an activating tyrosine kinase that is an effective equivalent to ZAK1, may antagonize canonical Wnt signaling and serve as a functional tumor suppressor.