FlyBase entry on NF1. - Bernards, A. (1998)
Subject: Flybase entry on NF1 Dear Sir: There are a few inaccuracies in the flybase entry on the Nf1 gene. The entry says that Nf1 is located at 96F11 and the map of the region places the gene telomeric to the E(spl) complex. In reality the Nf1 gene maps between the bride-of-sevenless and E(spl) loci at 96F (The et al., Science 276:791-794; 1997). The gene is transcribed from centromer to telomer (boss - 5' Nf1 3' - E(spl). Rather than mouse Nf1, the most obvious homolog of Nf1 is the human neurofibromatosis type 1 tumor suppressor gene. Biochemically, the human and fly NF1 proteins are GTPase activating proteins for Ras. However, Nf1 deficient phenotypes in Drosophila (reduced size, absence of a PACAP-induced rectifying potassium current at the larval neuromuscular junction) are not modified by manipulating Ras1 or Ras2 gene dosage, but rather are rescued by increasing signaling through the cAMP - PKA pathway. Thus, Nf1 functions either upstream of adenylyl cyclase or in a parallel pathway. Saying that Nf1 is a crucial component for activation of the cAMP pathway is overstating the case. I hope this was helpful. Please feel free to contact me if further information would be required. Best regards, Andre Bernards Andre Bernards Ph.D. Associate Professor of Medicine (Genetics) Massachusetts General Hospital Cancer Center Bldg. 149, 13th street Charlestown, MA 02129