Ras/MAP kinase pathway

Adaptor protein, containing one SH2 and two SH3 domains, which assembles signaling complexes at receptors. Particularly important for activation of the Ras-MAP kinase pathway. 

GGTase I may rescue the functions of some normally farnesylated proteins or redundant signaling pathways might be able to circumvent the Ras/MAP kinase pathway. 

It has been known for quite some time that signalling pathways controlled by growth factors and cytokines accept signals from heptahelical receptors, coupled to heterotrimeric G proteins. However, the individual steps that funnel hormonal signals via G-protein-coupled receptors and heterotrimeric G proteins into the Ras/MAP kinase pathway were not well defined. This state of affairs has changed recently. We now have an idea, although not yet complete, how hormones may contribute to the regulation of cell proliferation via G-protein-coupled receptors. 

Rg.6JL0 A possible route of communication between cytokine receptors and the RAS/MAP kinase pathway. The role of the MAP kinase in the phosphorylation of STAT is... 

Mainiero F, Murgia C, Wary KK, Curatola AM, Pepe A, Blumemherg M, Westwick JK, Der CJ, Giancotti FG. The cou-phng of alpha6heta4 integrin to Ras-MAP kinase pathways mediated hy She controls keratinocyte proliferation. EMBO J. 1997 16 2365-2375. 

Signal transduction (1) Ras-MAP kinase pathway (2) IP3/DAG pathway (3) PI-3 kinase pathway... 

The insulin receptor is a dimeric receptor tyrosine kinase that can initiate the Ras-MAP kinase pathway, leading to changes in gene expression. Insulin stimulation also can initiate the PT3 kinase pathway just described, leading to activation of protein kinase B. In insulin-stimulated liver, muscle, and fat cells, activated protein kinase B acts in several ways to lower blood glucose and promote glycogen synthesis. 

Interaction of different signaling pathways permits the fine-tuning of cellular activities required to carry out complex developmental and physiological processes. As we have noted previously, both RTKs and cytokine receptors can Initiate signaling via the Ras-MAP kinase pathway, DAG/IP3 pathway, and PT3 kinase pathway (see Table 14-1). In addition, cytokine receptors can act through their associated JAK kinases to direcdy activate STAT transcription factors. 

Activation of multiple signal-transduction pathways by many receptors allows different sets of genes to be Independently controlled by the same or different receptors. Occasionally these pathways can induce opposite effects. For example, genetic manipulation of the Ras-MAP kinase and PT3 kinase pathways during muscle differentiation indicates that these pathways have opposite phenotypic effects activation of the Ras-MAP kinase pathway inhibits myocyte differentiation into myotubes, whereas activation of the PT3 kinase pathway promotes it. 

Larijani, B., Allen-Baume V., Morgan, C.P., Li, M. and Cockcroft, S. (2003). EOF regulation of PITP dynamics is blocked by inhibitors of phospholipase C and of the Ras-MAP kinase pathway. Curr. Biol, 13 78-84. 

Oliveira, C.J., Schindler, R, Ventura, A.M., Morals, M.S., Aral, R.J., Debbas, V., Stem, A., and Monteiro, H.P. (2003). Nitric oxide and cGMP activate the Ras-MAP kinase pathway-stimulating protein tyrosine phosphorylation in rabbit aortic endothelial cells. Free Radic. Biol. Med. 55(4), 381-396. 

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