Mitogen activated protein kinase kinase (MKK) 3 and 6 are the main p38 mitogen-activated protein kinase activators in mammals. In the present study, three Atlantic salmon MKK6 orthologs were identified. The deduced amino acid sequences of the salmon MKK6 proteins were highly similar to mammalian MKK6 sequences, and they were ubiquitously expressed. All three were shown to be upstream activators of salmon p38.