Lymnaea EGF and gigantoxin I, novel invertebrate members of the epidermal growth factor family.
In this review, we compare the sequence and structural relationships of two epidermal growth factor (EGF) family related proteins that have recently been discovered in invertebrate species. The first is L-EGF, a secreted growth factor from the gastropod mollusk Lymnaea stagnalis. The second is a peptide toxin (Gigantoxin I), isolated from the sea anenome Stichodactyla giganteus, which can paralyze crabs. L-EGF and Gigantoxin I share striking sequence similarity with mammalian erbB1 receptor ligands, including most of the essential receptor binding sites. Intriguingly, L-EGF's tertiary structure resembles more the structure of the EGF-like domain of coagulation factors. That is, the secondary and tertiary structure of L-EGF indicates the presence of a double-stranded beta-sheet but also suggests that this protein, in contrast to all other erbB1 ligands, contains a calcium-binding domain. One of the most remarkable features of L-EGF and Gigantoxin I however, is the indication that these protein are synthesized as non-membrane bound secreted peptides. This feature sets L-EGF and Gigantoxin I apart from all other members of the EGF family or EGF-like proteins identified thus far. We discuss sequence similarities and dissimilarities in the light of indications that, despite the more than 600 million years of phylogenetic distance separating both these invertebrates from mammals, Gigantoxin I and L-EGF retain some affinity for the mammalian erbB-family of receptors. Considering that mammalian EGF and its family members are frequently implicated in neoplastic diseases, the increasing number of identified and characterized invertebrate EGF family members may provide valuable leads in the design of erbB receptor antagonists.
Hermann
P M
PM
Department of Physiology and Biophysics, Neuroscience Research Group, University of Calgary, Health Sciences Centre, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada.
Schein
C H
CH
Nagle
G T
GT
Wildering
W C
WC
D000818:Animals; D003064:Cnidarian Venoms; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000145:classification* / Q000378:metabolism*; D006801:Humans; D008195:Lymnaea / Q000378:metabolism*; D012615:Sea Anemones / Q000378:metabolism; D014118:Toxins, Biological / Q000737:chemistry / Q000145:classification / Q000378:metabolism*
D003064:Cnidarian Venoms; D014118:Toxins, Biological; C504109:gigantoxin I, Stichodactyla gigantea; D004815:Epidermal Growth Factor