Description
Product Characteristics: The MAPK (mitogen activated protein kinase) comprises a family of ubiquitous praline-directed, protein-serine/threonine kinases which signal transduction pathways that control intracellular events including acute responses to hormones and major developmental changes in organisms (1). This super family consists of stress activated protein kinases (SAPKs), extracellular signal-regulated kinases (ERKs), and p38 kinases, each of which forms a separate pathway (2). The kinase members that populate each pathway are sequentially activated by phosphorylation. Upon activation, p38 MAPK/SAPK2α translocates into the nucleus where it phosphorylates one or more nuclear substrates, effecting transcriptional changes and other cellular processes involved in cell growth, division, differentiation, inflammation, and death (3). Specifically p38 always acts as a pro-apoptotic factor with its activation leading to the release of cytochrome c from mitochondria and cleavage of caspase 3 and its downstream effector, PARP (4). p38 MAPK is activated by a variety of chemical stress inducers including hydrogen peroxide, heavy metals, anisomycin, sodium salicylate, LPS, and biological stress signals such as tumor necrosis factor, interleukin-1, ionizing and UV irradiation, hyperosmotic stress and chemotherapeutic drugs (5). As a result, p38 alpha has been widely validated as a target for inflammatory disease including rheumatoid arthritis, COPD and psoriasis (6) and has also been implicated in cancer, CNS and diabetes (7).
Target Information: The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response. Four alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]