MKK3 is a protein kinase that phosphorylates the p38 MAPK. Phosphorylation by MKK3 occurs on threonine and tyrosine residues and increases the activity of p38 to stimulate transcription factors ATF2 and Elk-1. MKK3, together with MKK6, serves as upstream regulators of p38 MAPK activation. A structural variant, MKK3b, has been identified that contains 29 more amino acids at its N-terminus.