MAPKAPK-2 is a serine/threonine protein kinase. This ~49 kDa member of the MAPKAPK family of protein kinases is also known as mitogen-activated protein kinase-activated protein kinase 2. MAPKAPK-2 is phosphorylated and activated by p38 MAP kinase in response to stress, cytokines and chemokines. MAPKAPK-2 is phosphorylated on multiple sites including Thr222, Ser272 and Thr334. Phosphorylation of any two of these three amino acid residues seems to be required for the activation of this kinase that serves multiple cellular functions. Mice deficient in MAPKAPK-2 have been shown to be protected from ischemic injury. MAPKAPK-2 is also reported to serve as a cell cycle checkpoint kinase in response to UV irradiation. The heat shock protein, HSP27 was shown to be one of the major substrates of MAPK and MAPKAPK-2.