5-lipoxygenase (5-LO) catalyzes the initial steps in the formation of leukotrienes, a group of inflammatory mediators derived from arachidonic acid (AA). Here we describe that activation of p38 mitogen-activated protein kinase in human polymorphonuclear leukocytes and in Mono Mac 6 cells leads to activation of downstream kinases, which can subsequently phosphorylate 5-LO in vitro. Different age...

BACKGROUND Mitogen-activated protein (MAP) kinases (or extracellular signal regulated kinases; Erks) and stress-activated protein (SAP) kinases mediate cellular responses to a wide variety of signals. In the Erk MAP kinase pathway, activation of MAP kinases takes place in the cytoplasm and the activated enzyme moves to the nucleus. This translocation to the nucleus is essential to MAP kinase si...

Many extracellular stimuli are converted into specific cellular responses through the activation of mitogen-activated protein kinase (MAPK) signalling pathways. MAPKs are serine/threonine protein kinases that can phoshorylate both cytoplasmic and nuclear targets.1,2 Four distinct subgroups within the MAP kinase superfamily have been described: extracellular signal-regulated kinases (ERKs), c-ju...

Mitogen-Activated Protein Kinase Cascades: Terminology and Properties The best-characterized subfamilies of the mitogen-activated protein kinase (MAPK) superfamily are the extracellularly responsive kinases (ERKs) and the two “stress-responsive” MAPK subfamilies, namely, the c-Jun N-terminal kinases (JNKs) and the p38-MAPKs. As yet, no single nomenclature has been determined, and the synonyms c...

soybean isoflavone genistein has multiple anticancer properties and its pro-apoptotic and anti-proliferative effects have been studied in different cancer cells. however, the mechanisms of action of genistein and its molecular targets on human colon cells have not been fully elucidated. therefore, caspase-3 and p38 mitogen-activated protein kinase (p38 mapk) as the main therapeutic targets were...

MAP kinase phosphatase-3 (MKP-3) dephosphorylates phosphotyrosine and phosphothreonine and inactivates selectively ERK family mitogen-activated protein (MAP) kinases. MKP-3 was activated by direct binding to purified ERK2. Activation was independent of protein kinase activity and required binding of ERK2 to the noncatalytic amino-terminus of MKP-3. Neither the gain-of-function Sevenmaker ERK2 m...

Inflammation is a natural host defensive process that is largely regulated by macrophages during the innate immune response. Mitogen-activated protein kinases (MAPKs) are proline-directed serine and threonine protein kinases that regulate many physiological and pathophysiological cell responses. p38 MAPKs are key MAPKs involved in the production of inflammatory mediators, including tumor necros...

Mycobacterium tuberculosis upregulates NF-kappaB binding and interleukin-8 (IL-8) gene expression and secretion in primary human monocytes. Inhibition of tyrosine protein kinases but not of ERK1/2 or p38 mitogen-activated protein kinases downregulates tuberculosis-induced IL-8 secretion. The inhibitor genistein decreased NF-kappaB nuclear translocation and IL-8 gene transcription in addition to...