Secreted Fringe-like Signaling Molecules May Be Glycosyltransferases

chance p ϭ 1.9x10 Ϫ7) to a putative secreted protein from Molecules May Be C. elegans (Figure 1) as well as to human and mouse Glycosyltransferases ESTs (blast p-values <10 Ϫ11). The two most conserved regions of all three subfamil-ies FNG, BRN, and Lex1 (motif 3 and 4 in Figure 1) are also the major hallmarks of the putative glycosyltransfer-Pattern formation during development requires the reg-ase superfamily (a more precise prediction of the sub-ulated expression of numerous signaling molecules. strate specificity is not possible given the limited se-One of these, Drosophila Fringe (FNG) is a novel sequence similarity between the subfamilies; Paulson and creted protein with a key role in dorsal-ventral aspects of Colley, 1989). In the context of an enzymatic function it wing formation (Irvine and Wieschaus, 1994). Recently, has to be noted that only negatively charged amino multiple functions have been assumed for a Xenopus acids are invariant, thus pointing to catalytic residues homologue (lunatic Fringe, lFNG) including the induction similar to those in characterized glycosyltransferase of mesoderm; a complex expression pattern supportsComplex and general functions of Fringe-like proteins ture predictions (Rost et al., 1994) that are consistent are also indicated by the presence of two divergent C. around all conserved regions (Figure 1) and that predict elegans and at least six human homologues identifiable the conserved negatively charged residues to be located by sequence database searches (Figure caption). Thus, in exposed loops indicating a catalytic role. The alternat-conservation patterns within the FNG family emerge that ing arrangement of ␣-helices and ␤ strands suggest an allow the use of sensitive motif and profile searches (for ␣/␤ folding type for the central portion of each subfamily, details see Bork and Gibson, 1996). Indeed, we found similar to that of other glycosyltransferases (Strokopy-significant similarities of FNG-like proteins to Drosophila tov et al. The conclusion that signaling molecules involved in to the Lex1 family of biosynthetic galactosyltransferases pattern formation such as Fringe and Brainiac, may be (Figure 1). secreted glycosyltransferases might come as a surprise, BRN has been proposed to be required for proper but is not completely unexpected: i) Glycosyltransfer-contact or adhesion between germline and follicle cells ases have been implicated in developmental processes (Goode et al., 1992,1996). BRN and FNG share several for a long time (Shur, 1977a,b); ii) many extracellular, features: i) they are developmentally regulated, secreted highly expressed glycosyltransferases have been shown signaling molecules without known receptors, …