MAP2K4 and ischemia: Protein kinase D (PKD) phosphorylation induced by ischemia stimulates phosphorylation of Hsp27, then phosphorylated Hsp27 binds to ischemia-activated (phosphorylated) apoptosis signal-regulating kinase1 (ASK1) and prevents ASK1 signaling through MKK4/7, c-Jun NH (2)-terminal kinase (JNK) and c-Jun, thereby inhibiting apoptosis and reducing infarct volume of cerebral ischemia [86, 89].