Parallel to the transcriptional regulation of ERK5 by GLI1, our data also indicate that activation of the HH-GLI pathway in either NIH/3T3 and melanoma cells induces a marked increase of ERK5 phosphorylation at MEK5 consensus residues (T218/Y220), likely through increasing the expression and phosphorylation of MEK5. This evidence concerns the gene GLI1 and melanoma.