Vertebrate EGF activates S. mansoni EGFR and the downstream classical ERK pathway, indicating the conservation of EGFR function in S. mansoni. Moreover, human EGF was shown to increase protein and DNA synthesis as well as protein phosphorylation in parasites, supporting the hypothesis that host EGF could regulate schistosome development. The selleck chem similarity of schistosome proteins to sex hormone receptors of mammalian hosts provides a good example of host parasite relationship, where the adult worm depends on the host hormone synthesis for their maturation and reproduction. Five S. mansoni proteins are not clustered with the main RTK families as shown in our phylogenetic analyses. Three of them have a truncated catalytic domain and two are specific RTK with a venus flytrap domain.

VKR is a family of receptors found in inver tebrates, especially in insects. One S. mansoni VKR pro tein, Smp 153500, was recently studied. We identified another protein clustering with SmVKR with a high similarity. Despite the similarity of the catalytic domain of VKR pro tein with the IRs, these two proteins are not clustered with InsR family. In this respect, the most interesting finding is that VKR family members are not found in mammals and could represent good targets for drug development as a specific inhibitor for this family will probably not affect any protein of the host. The CTKs in S. mansoni are represented by 11 different families. SmTK3 and SmTK5 src family members, and SmTK4 syk family, are present in reproductive organs and possibly involved in the development of gonads and multiplication of germinal and vitelline cells.

Abl proteins of S. mansoni were recently studied using a Abl specific inhibitor. The results showed an important morphological alteration in adult worms of S. mansoni that led to the death of the parasites. C. elegans contains 42 members of the Fer family, while only a single member, SmFes, was found in S. mansoni. The Fer gene of S. mansoni exhibits the characteristic features of Fes Fps Fer PTKs. By immunolocalization assays it was shown that SmFes is particularly expressed at the terebratorium of miracidia and tegument of cercaria and schistosomula skin stage. These findings suggest that SmFes may play a role in signal transduction pathways involved in larval transformation after penetration into intermediate and definitive hosts.

RGC group Proteins in this group share sequence similarity to the cat alytic domain found in proteins of the TK group. The RGC group is underrepresented in most species, except in C. elegans that has a large expan sion of these proteins and S. cerevisiae that has no protein with Brefeldin_A similarity to the TK catalytic domain. Only three RGC members were identified in the S. mansoni ePKinome. All of them are more closely related to the mammalian and insect families than the worm family. C. elegans and B. malayi RGC proteins form at least two different families noticeably more divergent from S. man soni, D.