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