Regulatory mediators proteins

Of particular interest for regulatory processes are mechanisms by which the activity of growth regulating proteins and central transcription factors are controlled via ubiquiti-nylation. Often the cell uses signal pathway mediated protein phosphorylation in order to induce the regulated degradation of a signal protein. Examples are the G1 cychns, the tumor suppressor p53 and the inhibitor IxB. 

It became more important to understand the channel properties of PC2 after it was found that a pathogenic missense mutation of PC2 (D511V), where a single amino acid in the third membrane-spanning domain is mutated, results in loss of PC2 channel activity (Koulen, Cai et al. 2002). This missense mutant retains its localization and C-terminal-mediated protein interaction and regulatory domains of the wild type protein, thus providing evidence that the loss of channel function alone is sufficient to cause PKD. 

Hence, regulatory G proteins help account for how drugs can bind to one type of receptor and stimulate cell function, whereas drugs that bind to a different receptor on the same cell can inhibit cell activity. G proteins also seem to be important in mediating the other cell responses to stimulation or inhibition. For instance, cell function may continue to be... 

As described in Chapter 4, regulatory G proteins act as an intermediate link between receptor activation and the intracellular effector mechanism that ultimately causes a change in cellular activity. In the case of opioid receptors, these G proteins interact with three primary cellular effectors calcium channels, potassium channels, and the adenyl cyclase enzyme.27 At the presynaptic terminal, stimulation of opioid receptors activates G proteins that in turn inhibit the opening of calcium channels on the nerve membrane.65 Decreased calcium entry into the presynaptic terminal causes decreased neurotransmitter release because calcium influx mediates transmitter release at a chemical synapse. At the postsynaptic neuron, opioid receptors are linked via G proteins to potassium channels, and... 

Substrate recognition and selection of the JNK/SAPK and p38 proteins (and also the ERK proteins) are mediated both by specific docking sites and by the nature of the amino acids surrounding the phosphoacceptor site. For the transcription factor substrates, specific docking domains have been identified that are loacted at a distance from the phosphorylation sites in the transactivation domain. These docking sites serve to increase the selectivity and specificity of phosphorylation, and they are used for recruitment of MAPK kinases into protein complexes at promotors, where they can phosphorylate other regulatory transcriptional proteins. 

Zhou, J., Zhai, Y., Mu, Y., Gong, H., Uppal, H., Toma, D., Ren, S., Evans, R. M., and Xie, W. (2006) A novel pregnane X receptor-mediated and sterol regulatory elementbinding protein-independent lipogenic pathway. J. Biol. Chem. 281,15013-15020. 

One well-established component of the intracellular cholesterol-transport system Is the steroidogenic acute regulatory (StAR) protein. This protein, which is encoded in nuclear DNA, controls the transfer of cholesterol from the cholesterol-rich outer mitochondrial membrane to the cholesterol-poor Inner membrane, where it undergoes the first steps in its enzymatic conversion into steroid hormones. StAR-mediated cholesterol transport Is a key regulated, ratecontrolling step in steroid hormone synthesis. StAR contains... 

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