Subject: p38c gene I am writing to express the opinion that the predicted gene p38c at 91E1-2 is not a third Drosophila p38/MAPK gene. This opinion is based on three observations. While the proximity and overall sequence homology of p38c to D-p38a does suggest a recent genomic duplication, two key changes in the genomic sequence make it impossible for this gene to code a functional MAPK. The most important of these is that the invariant p38 MAPK dual phosphorylation motif, TGY, has been changed to TDH in p38c (AA 177-179). This motif cannot serve as a substrate for dual phosphorylation. (The phosphorylation motifs for ERK and JNK are TEY and TPY, respectively.) Second, the 8 amino acid catalytic loop in p38c contains two changes, likely to render it nonfunctional (AA 144-151). Lastly, to date no ESTs have been found for this gene. Callie Craig Cagan Lab Department of Molecular Biology & Pharmacology Washington University School of Medicine 660 S. Euclid, Box 8103 St. Louis, MO 63110