Affiliations: Childrens Hospital Los Angeles Research Institute,
Department of Pediatrics, Keck School of Medicine, University of Southern
California, Los Angeles, CA 90027, USA | Department of Environmental Health Sciences,
University of Alabama at Birmingham, Birmingham, AL 35294, USA
Note: [] Corresponding author: Martine Torres, Ph.D. 4650 Sunset Blvd.,
M.S.57, Los Angeles, CA 90027, USA. E-mail: [email protected]
Abstract: The mitogen-activated protein (MAP) kinases are a large family of
proline-directed, serine/threonine kinases that require tyrosine and threonine
phosphorylation of a TxY motif in the activation loop for activation through a
phosphorylation cascade involving a MAPKKK, MAPKK and MAPK, often referred to
as the MAP kinase module. Three separate such modules have been identified,
based on the TxY motif of the MAP kinase and the dual-specificity kinases that
strictly phosphorylate their specific TxY sequence. They are the extracellular
signal regulated kinases (ERKs), c-jun N-terminal kinases (JNKs) and p38 MAPKs.
The ERKs are mainly associated with proliferation and differentiation while the
JNKs and p38MAP kinases regulate responses to cellular stresses. Redox homeostasis is critical for proper cellular function. While
reactive oxygen species (ROS) and oxidative stress have been implicated in
injury, a rapidly growing literature suggests that a transient increase in ROS
levels is an important mediator of proliferation and results in activation of
various signaling molecules and pathways, among which the MAP kinases. This
review will summarize the role of ROS in MAP kinase activation in various
systems, including in macrophages, cells of myeloid origin that play an
essential role in inflammation and express a multi-component NADPH oxidase that
catalyzes the receptor-regulated production of ROS.
Keywords: MAP kinase, signal transduction, redox signaling, thiols
Journal: BioFactors, vol. 17, no. 1-4, pp. 287-296, 2003
