Subject: CG8222/vgr1 and PDGF Dear Flybase, My lab is in the process of publishing a paper on the function of a receptor tyrosine kinase which is called 'vgr1' in Flybase and its ligand CG7103, a PDGF-related molecule which is annotated in a confusion way due to confusing Genbank submissions. We initially called the receptor DPR (for Drosophila PDGF Receptor related protein) and the ligand DPL1 (for Drosophila PDGF Like-1 \- there are two other putative ligands in the genome which we call DPL2 and DPL3). There are several reasons why I think the name vgr1 should not be used for the receptor (see below). I would prefer if we could agree on naming of receptor and ligand before publication and am therefore writing to you now. The receptor: By simple blast search with the 'VGR1' or CG8222 protein sequence, the mammalian PDGF-alpha receptor is the most closely related (e-73 versus e-53 for the most closely related VEGF Receptor). The number of extra-cellular Ig domains is more similar to VEGF receptor than to PDGF receptor. Thus the receptor is part of the PDGFR/VEGFR (super-)family but not orthologue of a particular receptor (same is true for the ligands, see below). Since PDGFR is better known than VEGFR and the ligands are identified by having a PDGF domain, a name reflecting this is appropriate. There is only one receptor in the fly genome corresponding to the whole family of mammalian PDGF receptors and VEGF receptors, thus calling it VGR1 is misleading. The Vgr1 sequence is only submitted to Genbank, no manuscript or abstract cited. We have data for both function and biochemical interaction with the ligand. Maybe DPR is not optimal \- perhaps we can compromise on PVR (for PDGF- and VEGF- Receptor related)? The ligands: They are defined by having a PDGF domain. We have biochemical data that what we call DPL1 (CG7103) binds to and activates DPR. Two additional predicted proteins with PDGF motifs are located at 27D-E on the second chromosome. RT-PCR analysis on ovary mRNA and sequencing of the product indicated that CG13780 is spliced to encode a PDGF domain protein (DPL2); CG13781 and CG13782 are spliced together to encode one PDGF domain protein (DPL3). This is noted in our manuscript. The ligands are predicted to have PDGF domains and are by sequence equally related to mammalian PDGFs and VEGFs. I think a name reflecting the connection to PDGF (and the PDGF domain) is most appropriate and the numbers useful as there appear to be several ligands (we and others have genetic evidence for related functions of the ligands). Again, the names can be changed but should not be 'VEGF'. Please let me know what the view of Flybase is. We will relatively soon submit the revised version of our manuscript. I know it is best for everyone if we agree on these things quickly. Thanks for your help. sincerely, Pernille Rorth Subject: Re: CG8222/vgr1 and PDGF Dear Pernille, thanks for your enquiry about 'Vgr1' (FBgn0032006) and its ligands. FBgn0032006 has the symbol 'Vgr1' because Christophe Roos named it VGR1 in GenBank/EMBL/DDBJ record AJ250859. The FlyBase gene record for this gene was brought into being labelled Vgr1 in line with our nomenclature policy about only the initial letter of the symbol named for a protein being capitalized. Your reasons for changing the symbol from Vgr1 seem eminently sensible. We could change the symbol/name for FBgn0032006 to Pvr (not currently being used for any other gene) or another unique symbol, but the new symbol/name needs to be agreed by Christophe. Ideally you and Christophe would send me a joint email asking for the symbol/name to be changed. This email would be kept as a personal communication from the both of you to FlyBase. I've enclosed Christophe's contact info from FlyBase for you. As far as the ligands go, it is entirely up to you how you re-name the CG genes, though beginning a Drosophila gene with D for Drosophila or Dm for D. melanogaster cannot be accommodated in FlyBase gene records. (I've enclosed an email we sent out about this some time ago \- for the sake of completion). Pvf1, Pvf2 and Pvf3 (for PDGF- and VEGF- related factor 1, 2 and 3) would be fine. We look forward to your paper because we enjoy seeing functions assigned to CGs, and merging CG records into one gene record to improve the annotation, whenever we can. All the best, Rachel. FlyBase Consortium. Subject: Re:CG8222 /vgr1 and PDGF Dear Rachel, I've just talked to Christophe Roos and he agrees that Pvr is a good name for CG8222/vgr1, reflecting that this receptor corresponds to mammalian PDGFR as well as VEGFR, and that there is only one such receptor. I asked him to send an Email to Flybase to confirm this agreement. Pvf1-3 then seems an appropriate name for the ligands. We will make the appropriate changes in our manuscript and hope that the names stick... Thanks for your help, Pernille Subject: Receptor and factor naming convention Subject: Gene Vgr1 (receptor) and three factors naming We have named these sequences primarily to enable operating with these genes/proteins. Since we for the moment have no really solid clue as to their function, I am not trying to impose any naming and would be glad to agree to a common and more sensible nomenclature. Now, Pernille Rorth has contacted me on this matter, since she has been working on the same genes and is now submitting an article on the studies. In a correspondence with Flybase (Rachel Drysdale (Genetics) .., Aug. 15th 2001), Pernille has made a naming proposal to which I am ready to agree if FlyBase considers this sensible. This is the present status: code / presently / EMBL AC / proposed \-------------------------------------------- CG7103 / DmVEGF-1 / AJ401391 / Pvf1 CG8xxx / DmVEGFR / AJ250859 / Pvr CG13780 / DmVEGF-2 / AJ312312 / Pvf2 CG13782 / DmVEGF-3 / \- / Pvf3 We have a paper in press where all these molecules are discussed. As soon as the coordinates are known, I can update EMBL and FlyBase. So far, if you (FlyBase) consider this naming convention appropriate, I can do the updates in the EMBL entries, while you will probably do them in FlyBase. Please let me know how to proceed. Thank you very much for keeping our very valuable FlyBase up to date. Sincerely Christophe Christophe Roos Dr.Sc, doc., MediCel Biomedicum, Haartmansg. 8 (PL63), FIN-00290 Helsinki