Molecular characterisation of MEK1/2- and MKK3/6-like mitogen-activated protein kinase kinases (MAPKK) from the fox tapeworm Echinococcus multilocularis

The role of evolutionarily conserved signalling systems in Echinococcus multilocularis development and host–parasite interaction

“…14-3-3 proteins usually act as scaffolds in regulating proteinprotein interaction and are well-established interaction partners of Raf-like MAPKKKs in mammals [50]. Interestingly, we could recently demonstrate that one of the E. multilocularis 14-3-3 isoforms, Em14-3-3.2, interacts with EmMKK2, which forms part of the Erk-like MAPK cascade [45]. Since PDZ-domain-containing proteins can act as linkers between RTKs such as the EGF receptor and cytoskeleton elements [51], the so far only known member of this family in E. multilocularis, EmPDZ-1, could fulfil a similar role between EmER and the ezrin-radixin-moesin family component Elp [49].…”

“…Further, MAPK cascade signalling components that we have identified are the small GTPase EmRal [46], the MKK3/6-like MAPKK EmMKK1 [45] and the p38-like MAPK EmMPK2 [47]. Although it became clear from biochemical analyses than none of these components forms part of the parasite's Erk-like MAPK pathway [45][46][47], further investigations are necessary to define the MAPK cascade pathways in which they participate. Finally, members of the 14-3-3 and the PDZ-1-domain containing protein families were described in E. multilocularis [48,49] that could both be involved in RTK signalling events.…”

“…1 Schematic representation of the E. multilocularis Erk-like MAPK module and its activation through host-derived EGF. Direct interactions between EmRas and EmRaf, EmRaf and EmMKK2, as well as EmMKK2 and EmMPK1 have been demonstrated by yeast two-hybrid studies [43,45]. Inhibition of EmRaf through BAY 43-9006 or EmMKK2 through PD 184352 leads to de-phosphorylation of EmMPK1 and growth arrest [47].…”

“…EGF-and FGF-like signals are typically transmitted from the cell surface to the nucleus via Erk-like mitogen-activated protein kinase (MAPK) modules that, in mammals, comprise small GTPases of the Ras-family, Raflike MAPK kinase kinases (MAPKKK), the two MAPK kinases (MAPKK) MEK1 and MEK2, and the MAPKs Erk1 and Erk2 [42]. In the E. multilocularis genome, one member of each of these signalling molecule families is encoded, and RT-PCR experiments as well as recent transcriptome analyses indicated that the respective genes are expressed throughout the E. multilocularis life cycle [43][44][45]. Furthermore, by biochemical analyses, we could show that the GTPase EmRas, the Raf-like MAPKKK EmRaf, the MEK1/2-like MAPKK EmMKK2 and the Erk1/2-like MAPK EmMPK1 form a functional MAPK module [43,45] that acts downstream of EmER [44,45] and EmFR (Lorenz et al, unpublished data) (Fig.…”

Identification of genetic loci affecting the establishment and development of Echinococcus multilocularis larvae in mice

“…Meanwhile, several host-derived molecules were previously reported to exist in the cyst fluid or on the wall (Kassis and Tanner, 1977;Ali-Khan and Siboo, 1981), indicating that certain host-derived factors are transported through the laminated layer and are involved in parasite development in the hosts. In recent years, great progress has been made in elucidating the mechanisms of parasite development in the hosts by identifying the evolutionarily conserved signaling systems in E. multilocularis, which can interact with hostderived molecules (Konrad et al, 2003;Spiliotis et al, 2003Spiliotis et al, , 2005Spiliotis et al, , 2006Zavala-Góngora et al, 2003Gelmedin et al, 2008Gelmedin et al, , 2010Brehm, 2010;Förster et al, 2011). Specifically, interactions between parasite receptors and host-derived molecules, such as epidermal growth factor and insulin have been demonstrated experimentally (Spiliotis et al, 2006;Gelmedin et al, 2008;Brehm, 2010), strongly suggesting that parasite development is triggered by host signaling systems.…”