The MAPK (mitogen activated protein kinase) comprises a family of ubiquitous praline-directed, proteinserine/
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).