A Drosophila genomic sequence with homology to human epidermal growth factor receptor

Abstract

Vertebrate genomes contain an extensive family of genes possessing varying degrees of homology to the v-src oncogene. Most src-related proteins identified to date are intracellular and membrane-associated, although some are transmembrane proteins and function as receptors for peptide growth factors. Three Drosophila gene sequences related to the v-src gene have been identified, each exhibiting a high degree of homology to one or more of the src-family members encoding an intracellular protein. We have isolated a panel of cloned Drosophila sequences exhibiting weak v-src hybridization and were interested to determine whether any members of this group represented homologues of additional known src-family genes, especially those functioning as growth factor receptors. As we report here, four of these clones, representing overlapping portions of the same genomic segment, hybridized preferentially with the v-erb-B oncogene and were further characterized. The deduced amino-acid sequence from a portion of this Drosophila genomic segment is 77% homologous to the kinase domain of human epidermal growth factor (EGF) receptor, a substantially greater degree of homology than was observed with any other known src-family member. By hybridization with a human EGF receptor complementary DNA clone probe, we demonstrate that the same genomic segment showing homology with the kinase domain also contains sequences related to the extracellular domain of the EGF receptor gene.

Drosophila melanogaster homologs of the raf oncogene.

“…Multiple spliced and terminated forms of the c-abl homolog Dash have been identified in unfertilized eggs and ovaries as 5.5-to 6.0-kb and 3.0-kb RNA species (17,34) and during all but the late larval stage of development (34). Finally, transcripts representing the epidermal growth factor receptor homolog (6.0 kb) were detected in embryonic, pupal, and adult tissues (36). Thus, common to all the src family gene products is their presumed participation in early developmental events.…”

windbeutel,a gene required for dorsoventral patterning inDrosophila,encodes a protein that has homologies to vertebrate proteins of the endoplasmic reticulum

“…Initially, the oocyte sends a dorsalizing signal to the follicle cells. This signal is received by the follicle cells via Egfr, the Drosophila homolog of the human epidermal growth factor receptor (Wadsworth et al 1985;Price et al 1989;Schejter and Shilo 1989). Egfr, which is expressed in the follicle cells, is believed to be locally activated by Gurken (Grk), a TGF␣ type molecule, produced by the oocyte (Neuman-Silberberg and Schü pbach 1993).…”

Primary sequence and developmental expression of a novel Drosophila melanogaster src gene.

“…6a through d). As a control for nonspecific binding of probe, in situ hybridizations were performed with antisense RNA transcripts from the Drosophila epidermal growth factor receptor homolog (14,29). This probe hybridizes to ovarian tissue in a pattern complementary to that observed with probes specific for Dsrc28C ( Fig.…”

“…The cloned DNA was truncated at the polylinker Sall site before in vitro transcription with SP6 RNA polymerase, according to the instructions provided by the manufacturer, to produce a 0.6-kb RNA probe. To construct the Drosophila epidermal growth factor receptor transcription template, a 3.5-kb EcoRI-HindIII genomic fragment containing virtually all of the amino acid coding sequences (29) was cloned into the Riboprobe pSP65 vector.…”