Mitogen-activated protein kinases (MAPKs) are important signal transducing enzymes, unique to eukaryotes, that are involved in many facets of cellular regulation. Initial research concentrated on defining the components and organization of MAPK signalling cascades, but recent studies have begun to shed light on the physiological functions of these cascades in the control of gene expression, cell proliferation and programmed cell death.

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Mammalian MAP kinase signalling cascades

Mitogen-activated protein (MAP) kinases comprise a family of ubiquitous proline-directed, protein-serine/threonine kinases, which participate in signal transduction pathways that control intracellular events including acute responses to hormones and major developmental changes in organisms. MAP kinases lie in protein kinase cascades. This review discusses the regulation and functions of mammalian MAP kinases. Nonenzymatic mechanisms that impact MAP kinase functions and findings from gene disruption studies are highlighted. Particular emphasis is on ERK1/2.

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Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions.

The molecular details of mammalian stress-activated signal transduction pathways have only begun to be dissected. This, despite the fact that the impact of these pathways on the pathology of chroni...

Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation

Widmann, Christian, Spencer Gibson, Matthew B. Jarpe, and Gary L. Johnson. Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human. Physiol. Rev. 79: 143–180, 19...

Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human

The transcription factor AP-1 (activator protein-1) is involved in cellular proliferation, transformation and death. Using mice and cells lacking AP-1 components, the target-genes and molecular mechanisms mediating these processes were recently identified. Interestingly, the growth-promoting activity of c-Jun is mediated by repression of tumour suppressors, as well as upregulation of positive cell cycle regulators. Mostly, c-Jun is a positive regulator of cell proliferation, whereas JunB has the converse effect. The intricate relationships between the different Jun proteins, their activities and the mechanisms that mediate them will be discussed.

AP-1 as a regulator of cell life and death

For cells of the innate immune system to mount a host defence response to infection, they must recognize products of microbial pathogens such as lipopolysaccharide (LPS), the endotoxin secreted by Gram-negative bacteria. These cellular responses require intracellular signalling pathways, such as the four MAP kinase (MAPK) pathways. In mammalian cells the MAPK p38 is thought to play an important role in the regulation of cellular responses during infection through its effects on the expression of proinflammatory molecules. One means of understanding the role of p38 in these responses is to identify proteins with functions regulated by p38-catalysed phosphorylation. Here we demonstrate a link between the p38 pathway and a member of the myocyte-enhancer factor 2 (MEF2) group of transcription factors. We found that in monocytic cells, LPS increases the transactivation activity of MEF2C through p38-catalysed phosphorylation. One consequence of MEF2C activation is increased c-jun gene transcription. Our results show that p38 may influence host defence and inflammation by maintaining the balance of c-Jun protein consumed during infection.

Zhuangjie Li

Papers

Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation.

Characterization of the Structure and Function of a New Mitogen-activated Protein Kinase (p38β)

Characterization of the structure and function of a novel MAP kinase kinase (MKK6)

The primary structure of p38 gamma: A new member of p38 group of MAP kinases

Apoptosis signaling pathway in T cells is composed of ICE/Ced-3 family proteases and MAP kinase kinase 6b