Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis (By similarity). ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein] Interacts with PARD6A, MAP3K3 and MAPK7. Forms a complex with SQSTM1 and PRKCZ or PRKCI (By similarity). The alternatively spliced exon in alpha isoform resemble conserved sequences that mediate interactions with the cytoskeleton, thereby explaining the differential localization. The alternatively spliced exon in alpha isoform resemble conserved sequences that mediate interactions with the cytoskeleton, thereby explaining the differential localization. MEK5 beta is ubiquitously distributed with highest levels in the liver, whereas MEK5 alpha is expressed only in liver and brain. Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues of the PB1 domain. This domain also mediates interactions with SQSTM1 and PARD6A (By similarity). Activated by phosphorylation on Ser/Thr by MAP kinase kinase kinases. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.