Mitogen activated protein kinases signaling cascade

Role of MLK3 in the regulation of mitogen-activated protein kinase signaling cascades. Mol CellBiol25, 3670-3681. 

Having introduced Ras, the master switch of the MAP kinase (mitogen-activated protein kinase) signalling cascades, we are now ready to put the pieces of the puzzle together and sum up the essential features of a typical cellular signalling pathway, the Ras/MAP kinase... 

Abraham ST, Benscoter HA, Schworer CM, Singer HA (1997) A role for Ca /calmodulin-dependent protein kinase II in the mitogen-activated protein kinase signaling cascade of cultured rat aortic vascular smooth muscle cells. Circ Res 81 575-584... 

Mandal, C., A. Dutta, A. Mallick, et al. 2008. Withaferin A induces apxjptosis by activating p38 mitogen-activated protein kinase signaling cascade in leukemic cells of lymphoid and myeloid origin tiuough mitochondrial death cascade. Apoptosis 13 (12) 1450-1464. 

Perkinton MS, Sihra TS, Williams RJ. Ca(2+)-permeable AMPA receptors induce phosphorylation of cAMP response element-binding protein through a phospha-tidylinositol 3-kinase-dependent stimulation of the mitogen-activated protein kinase signaling cascade in neurons. J Neurosci 1999 19(14) 5861-5874. 

Pierce, R.C., Pierce-Bancroft, A.F., Prasad, B.M. Neurotrophin-3 contributes to the initiation of behavioral sensitization to cocaine by activating the Ras/Mitogen-activated protein kinase signal transduction cascade. J. Neurosci. 19 8685, 1999. 

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. 

Tolan, D., Conway, A-M., Rakhit, S., Pyne, N.J. and Pyne, S., 1999, Assessment ofthe extracellular and intracellular actions of sphingosine 1-phosphate by using the p42/p44 mitogen-activated protein kinase cascade as a model. Cell. Signal. 11 349-354. 

Figure 21.9 The mitogen-activated protein kinase cascade (MAP kinase cascade). The active protein Ras activates Raf by promoting its recruitment to a cell membrane. Through a series of phosphorylations MAP kinase is activated as follows MAP kinase kinase kinase (Raf) phosphorylates MAP kinase kinase which, in turn, phosphorylates MAP kinase, the final target enzyme. MAP kinase phosphorylates transcription factors for genes that express proteins involved in proliferation. Another nomenclature for the enzymes is also used raf is MEKK MAPKK is MEK and finally ERK is MAP kinase (ERK is the abbreviation for extracellular-signal-related kinase) For comparison, the reader is referred to the metabolic phosphorylase cascade, which is discussed in Chapter 12 (Figure 12.12).

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

---