Cascades, kinase mitogen-activated

Figure 11-13 (A) A simplified version of the mitogen-activated kinase (MAPK) signaling cascade. At left is shown a hormone receptor, e.g., that for the epidermal growth factor (EGF). The receptor tyrosine kinase undergoes autophosphorylation on numerous tyrosines. The resulting phosphotyrosyl (Y-P) groups bind to SH2 domains of adapters such as Grb2 and She.

Stimulation of the insulin receptor results in the activation of two major pathways [3] (i) the mitogen-activated protein (MAP) kinase cascade (discussed in chapter MAP kinase cascade) and (ii) the phospha-tidylinositol 3-kinase (PI 3-kinase) pathway which has been extensively studied in the context of the metabolic responses to insulin (summarized in Table 1 and Fig. 2). 

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. 

Mitogen activated protein kinase. MAP Kinase Cascade... 

Dineley, K.T., Westerman, M., Bui, D., Bell, K., Ashe, K.H., Sweatt, J.D. Beta-amyloid activates the mitogen-activated protein kinase cascade via hippocampal alpha7 nicotinic acetylcholine receptors in vitro and in vivo mechanisms related to Alzheimer s disease. J. Neurosci. 21 4125, 2001. 

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. 

The kinases themselves can be arranged into phosphorylation cascades so that one kinase phosphorylates another, which, in turn, phos-phorylates another. This often leads to some funny names, such as MAP kinase kinase kinase. This means a mitogen-activated protein kinase that phosphorylates MAP kinase kinase. The activated MAP kinase kinase then phosphorylates and activates MAP kinase. 

The mitogen-activated protein kinase cascade is second-messenger-independent 396... 

The mitogen-activated protein kinase cascade is second-messenger-independent. Although the second-messenger-dependent protein kinases were identified first as playing an important role in neuronal function, we now know that many other types of protein serine-threonine kinase are also essential (Table 23-1). Indeed, one of the most critical discoveries of the 1990s was the delineation of the mitogen-activated protein kinase (MAP kinase or MAPK) cascades. 

Mori-Abe A, Tsutsumi S, Takahashi K, Toya M, Yoshida M, Du B, Kawagoe J, Naka-hara K, Takahashi T, Ohmichi M, Kurachi H (2003) Estrogen and raloxifene induce apoptosis by activating p38 mitogen-activated protein kinase cascade in synthetic vascular smooth muscle cells. J Endocrinol 178 417-426... 

Figure 10.6 Schematic representation of the mitogen-activated protein kinase (MAP) cascades in mammalian cells. (From Voet and Voet, 2004. Reproduced with permission from John Wiley Sons., Inc.)...

Moeigughi, T., et al., A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3. J Biol Chem, 1996, 271(23), 13675-9. 

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. 

Ge Z, Liu C, Bjorkholm M, Gruber A, Xu D (2006) Mitogen-activated protein kinase cascade-mediated histone H3 phosphorylation is critical for telomerase reverse transcriptase expression/telomerase activation induced by proliferation. Mol Cell Biol 26(l) 230-237 Giet R, Glover DM (2001) Drosophila aurora B kinase is required for histone H3 phosphorylation and condensin recruitment during chromosome condensation and to organize the central spindle during cytokinesis. J Cell Biol 152(4) 669-682... 

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 effects of insulin on transcription are shown on the left of the illustration. Adaptor proteins Crb-2 and SOS ( son of sevenless ) bind to the phosphorylated IRS (insulin-receptor substrate) and activate the G protein Ras (named after its gene, the oncogene ras see p.398). Ras activates the protein kinase Raf (another oncogene product). Raf sets in motion a phosphorylation cascade that leads via the kinases MEK and ERK (also known as MARK, mitogen-activated protein kinase ) to the phosphorylation of transcription factors in the nucleus. 

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