DLK, PG2 AND PREF-1 MESSENGER-RNAS ENCODE SIMILAR PROTEINS BELONGING TO THE EGF-LIKE SUPERFAMILY - IDENTIFICATION OF POLYMORPHIC VARIANTS OF THIS RNA

dlk encodes a transmembrane protein member of the EGF-like family of h omeotic proteins, dlk is expressed in the same type of neuroendocrine tissues and tumors as pG2, a gene cloned because of its differential e xpression in human pheochromocytomas versus neuroblastomas. Human dlk and pG2 cDNAs are around 98% similar in sequence, but the predicted pr oteins encoded by those genes are apparently unrelated. This fact sugg ested the existence of polymorphic variants of the same gene. We have sequenced again several pG2 and dlk clones in parallel. We identified a pG2 cDNA species corresponding to an alternatively spliced dlk mRNA, as well as several other variant forms of dlk mRNA. One of the pG2 cl ones resulted to be identical to human dlk and encode the same EGF-lik e protein. Pref-1, a cDNA. isolated from 3T3-L1 fibroblasts, encodes a putative protein possessing an extracellular EGF-like domain similar to dlk, but a different intracellular region. Analysis of sequence dat a from different clones obtained in our laboratory confirmed some of t he differences between dlk and Pref-1. However, the putative differenc e in the intracellular regions of dlk and Pref-1 was due to sequence a rtifacts. These data suggest that dlk, pG2 and Pref-1 are variant prod ucts of the same gene.