Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. 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] Activated by dual phosphorylation on Ser-218 and Thr-222. Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and ZAK (PubMed:21224381). Binds to DYRK1B/MIRK and increases its kinase activity (PubMed:11980910). Part of a complex with MAP3K3, RAC1 and CCM2 (By similarity). Interacts with ARRB1 (PubMed:16709866). (Microbial infection) Interacts with Yersinia YopJ. Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues. Autophosphorylated. Phosphorylation on Ser-218 and Thr-222 by MAP kinase kinase kinases regulates positively the kinase activity (PubMed:8622669). Phosphorylated by TAOK2 (PubMed:11279118). (Microbial infection) Yersinia YopJ may acetylate Ser/Thr residues, preventing phosphorylation and activation, thus blocking the MAPK signaling pathway. Defects in MAP2K3 may be involved in colon cancer. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.