Mitogen-activated protein kinase MAPK cascade

Mitogen-activated protein kinase (MAPK) cascades were among the first signaling pathways demonstrated to be activated by ROS. These effects have since been extensively investigated. Here, a brief overview on MAPK properties will be followed by a summary of the known physiological roles of MAPK and a paragraph on the mechanisms and consequences of activation of MAPK cascades by ROS. 

Mitogen activated protein kinase (MARK) cascades are three kinase modules activated by phosphorylation. The three kinase modules are composed of a MAPK, a MAPKK, and a MAPKKK. There are multiple members of each component of the MAPK cascade that are conserved from yeast to human. Activation of selective MAPK modules by specific stimuli regulates cell functions such as gene expression, adhesion, migration, differ entiation, and apoptosis. 

The SOS guanine-nucleotide exchange factor mediates GTP loading of Ras (Fig. 2), leading to activation of evolutionarily conserved effector proteins, such as the Raf ser-ine/threonine kinase, P13 K, and Ral-GDS. Raf activation triggers a cascade of phosphorylation events that lead to mitogen-activated protein kinase (MAPK) activation. 

The A3 Receptor and the Mitogen-Activated Protein Kinases (MAPKs) Signal Transduction Cascade... 

A recently identified thyroid hormone cell surface receptor on the extracellular domain of integrin alphaVbeta (3) leads to the activation of the mitogen-activated protein kinase (MAPK) signal transduction cascade in human cell lines, Examples of MAPK-dependent thyroid hormone actions are plasma membrane ion pump stimulation and specific nuclear events, These events include serine phosphorylation of the nuclear thyroid hormone receptor, leading to co-activator protein recruitment and complex tissue responses, such as thyroid hormone-induced angiogenesis, The existence of this cell surface receptor means that the activity of the administered hormone could be limited through structural modification of the molecule to reproduce only those hormone actions initiated at the cell surface (8,9). 

Figure 3 The MARK cascade. A signaling cascade generally refers to a series of enzyme modification processes, as in the activation of extracellular signal-regulated kinase (Erk) isoforms, which are mammalian mitogen-activated protein kinases (MAPKs). The first kinase, Raf, is activated (indicated by an asterisk) by numerous inputs, allowing it to phosphorylate MEK on two sites Erk is phosphorylated dually in a similar fashion by MEK. Each phosphorylation event is thought to require a separate encounter between enzyme and substrate, which gives rise to interesting dynamical properties. Not depicted here, but equally important, are the phosphatases that catalyze the reverse reactions.

MAPKs are a family of well-conserved serine/threonine kinases that have a central role in a wide variety of protein kinase cascades. These cascades consist of three kinases, a mitogen activated protein kinase (MAPK), a MAPK kinase (MAPKK) and a MAPK kinase kinase (MAPKKK), which modulate each other in a chain reaction. In other words, MAPKKK activates MAPKK which in turn activates MAPK. 

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