MAP Kinases signal transduction pathways

Wartmann M, Campbell D, Subramanian A, Burstein SH, Davis RJ (1995) The MAP kinase signal transduction pathway is activated by the endogenous cannabinoid anandamide. FEBS Lett 359(2-3) 133-6... 

Proliferative effects of homocysteine have been demonstrated in several in vitro studies. Brown et al. (61) found that homocysteine activates the MAP kinase signal transduction pathway in vascular smooth muscle cells. 

Z4. Zhu, X., and Liu, J. R, Steroid-independent activation of androgen receptor in androgen-independent prostate cancer A possible role for the MAP kinase signal transduction pathway Mol. Cell. Endocrinol. 134, 9-14 (1997). 

Each of these pathways involves a kinase cascade resulting in the phosphorylation and activation of the MAP kinase family member. Each contains a dual phosphorylation site (TEY, TPY, or TGY) and the central residue in the motif characteristic of the class, as shown in Table 8.1. It is evident that cells are endowed with parallel signal-transduction pathways and that they may operate individually or in combination to initiate specific patterns of gene expression. Additionally, crosstalk between the pathways undoubtedly occurs. None of these pathways has a unique function it is more likely that the combination of pathways that are activated (or silenced) together with the... 

FIGURE 8.6 Parallel pathways to transcription and the MAP kinase family. The MAP kinases can be classified into three groups, based on the identity of the intermediate residue in their dual phosphorylation motifs (TEY, TGY, or TPY). This classification also defines three distinct signal-transduction pathways indicated as the ERK, the JNK/SAPK, and the p38/HOG pathway, each having unique protein kinases acting upstream. 

One of the downstream elements of the signal transduction pathway, MAPKK (or, MEK) is phosphorylated by a Ser/Thr protein kinase, known as Raf, and phosphorylated MAPKK then catalyzes phosphoryl transfer to MAP kinase. The following is a recent review on the molecular and physical properties of this phosphotransferase (or, MAP kinase kinase). 

Figure 6.19. Examples of osmosensory signal transduction pathways in Escherichia coli (A) and the yeast Saccharomyces cerevisiae (B). In both species, the primary osmosensors (KdpD, SLN1, and Shol) are transmembrane proteins. Components of the signal transduction pathways (KdpE, SSK1, and HOG1 MAP kinase cascade) are interspersed between the primary osmosensors and the chromosomes. Note that the yeast HOG1 MAP kinase cascade contains at least seven different proteins, which have been omitted from the diagram for clarity. (Figure courtesy of Dr. Dietmar Kiiltz.)...

Fig. 2 Outline of signal transduction pathways for stress kinases, JNKs, and for Map kinases, p38 and ERKl/2. Shown is the cross-talk between the various pathways. Map kinases MEKKl/2/3 activate the MAP kinases MKK4 (JNKKl) and MKK7 (JNKK2). MKK4/7 can also be activated by the Map kinases TAKl and Askl, which can also activate MKK3/6 of the p38 s pathway. Activation of Rap-GTP is capable of activating the p38 and ERKl/2 pathways. As indicated, ceramide can activate the p38 pathway, and, also, has been suggested to play a role in activation of the ERKl/2 pathway...

Althou the role of the MAP kinase phosphorylation cascade in the control of cell growth and cellular proliferation is undisputed, other pathways and pathway ramifications contribute to that control. This requires communication between signal transduction pathways. MAP kinase also seems to play a part in pathway interconnections, for example in connecting signals from G-protein-coupled receptors with signals from growth-factor-activated receptors (discussed in Chapter 5). 

NISHIDA E, GOTOH Y. The MAP kinase cascade is essential fev diverse signal transduction pathways. Trends Biol Sd 10 128-131,1993. 

The intracellular signal transduction pathway by which the yeast [16, 17] Saccharomyces cerevisiae responds to the presence of peptide mating pheromone in its surroundings is one of the best understood signalling pathways in eukaryotes, yet continues to generate new surprises and insights. The signal is transmitted from the cell-surface receptor-coupled G protein, via a MAP kinase cascade, to the nucleus. 

Phosphorylation of one or more residues in a conserved lip region activates MAP kinases and many other protein kinases involved in signal-transduction pathways. 

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