Receptor/G protein

Figure 13.2 Activated G protein receptors, here represented as seven red transmembrane helices, catalyze the exchange of GTP for GDP on the Gapy trimer. The then separated Ga-GTP and Gpy molecules activate various effector molecules. The receptor is embedded in the membrane, and Ga, Gpy and G py are attached to the membrane by lipid anchors, and they all therefore move in two dimensions. (Adapted from D. Clapham, Nature 379 297-299, 1996.)...

At a cellular level, the activation of mAChRs leads to a wide spectrum of biochemical and electrophysiological responses [1, 5]. The precise pattern of responses that can be observed does not only depend on the nature of the activated G proteins (receptor subtypes) but also on which specific components of different signaling cascades (e.g. effector enzymes or ion channels) are actually expressed in the studied cell type or tissue. The observed effects can be caused by direct interactions of the activated G protein(s) with effector enzymes or ion channels or may be mediated by second messengers (Ca2+, DP3, etc.) generated upon mAChR stimulation. 

Figure 3.4 Transmembrane topology of a 7-TM domain G-protein receptor such as the P-adrenoceptor. Agonist binding is predicted to be within the transmembrane domains. The extracellular structure is stabilised by the disulphide bond joining the first and second extracellular loop. The third intracellular loop is the main site of G-protein interaction while the third intracellular loop and carboxy tail are targets for phosphorylation by kinases responsible for initiating receptor desensitisation...

One current model of G-protein receptor activation is the allosteric ternary complex model of Lefkowitz and Costa. The agonist, receptor and G-protein must combine to... 

G protein Receptor subtype Second messenger system... 

The carboxy terminus of the ft receptor was essential for agonist-induced desensitization [83, 132] since truncation of the receptor prevented desensitization. Like those findings with the k receptor, the enzyme G protein receptor kinase (GRK) appears to be involved in the desensitization process, since blockade of GRK prevented the desensitization process. Wang [132] has proposed that GRK catalyzes the phosphorylation of a series of serine/threonine residues in the C-terminus of the fi receptor to desensitize the receptor. 

Agonist-dependent desensitization of the kappa opioid receptor by G protein receptor kinase and beta-arrestin. J Biol Chem 1999 274 233802-233807. 

Blumer, J. B. and Lanier, S. M. Accessory proteins for G protein-signaling systems activators of G protein signaling and other nonreceptor proteins influencing the activation state of G proteins. Receptors Channels 9 195-204, 2003. 

CDK, cyclin-dependent kinase ERK, extracellular signal-regulated kinase GRK, G protein receptor kinase JNK, Jun kinase MAP kinase, mitogen activated protein kinase MEK, MAP kinase and ERK kinases RSK, ribosomal S6 kinase, GSK, glycogen synthase kinase SAPK, stress-activated protein kinase SEK, SAPK kinase. 

The brain contains many other types of second-messenger-independent protein kinases. Examples of other second-messenger-independent protein kinases are listed in Table 23-1. Many of these include enzymes that were identified originally in association with a particular substrate protein but shown later to play a more widespread role in brain signal transduction. The functional role of one of these, [3-adrenergic receptor kinase (PARK), a type of G protein receptor kinase (GRK), is discussed further below. 

Other mechanisms have also been implicated in odor adaptation, including cAMP-dependent phosphorylation of ciliary proteins via protein kinase A G-protein-receptor kinase activity (GRK3), possibly via phosphorylation of the OR Ca2+/calmodulin kinase II (CaMKII) phosphorylation of ACIII cGMP and carbon monoxide [ 31 ]. These latter three mechanisms have been particularly linked to longer-lasting forms of adaptation, on the order of tens of seconds (for CaMKII) or minutes (CO/cGMP). Together with the short-term adaptation described above, these various molecular mechanisms provide the OSN with a number of ways to fine-tune odor responses over time. 

EFTU eukaryotic elongation factor GRK G protein receptor kinase... 

Lichtarge, O., Bourne, H. R., and Cohen, F. E. (1996) Evolutionarily conserved Galpha-betagamma binding surfaces support a model of the G protein-receptor complex. Proc. Natl. Acad. Sci. USA 93, 7507-7511. 

Spiegel, A. M. (1998) Introduction to G-protein-coupled signal transduction and human disease, in G proteins, receptors, and disease (A. M. Speigel, ed.), Humana Press, Totowa, NJ,... 

J. A. Koenig, J. Edwardson (1997). Endocytosis and recychng of G protein receptors. Trends... 

Alpha receptors There are two major groups of alpha receptors, and a. Activation of postsynaptic receptors increases the intracellular concentration of calcium by activation of a phospholipase G in the cell membrane via G protein, receptor is responsible for inhibition of renin release from the kidney and for central a-adrenergically mediated blood pressure depression. 

Martin, E. L., Rens-Domiano, S., Schatz, P.J., and Hamm, H. E. (1996). Potent peptide analogues of a G protein receptor-binding region obtained with a combinatorial library. / Biol. Chem. 271, 361-366. 

O Dowd, B. F., Hnatowich, M., Regan, J. W., Leader, W. M., Caron, M. G., and Lefkowitz, R. J. (1988). Site-directed mutagenesis of the cytoplasmic domains of the human / 2-adrenergic receptor. Localization of regions involved in G protein-receptor coupling. / Biol. Chem. 263, 15985-15992. 

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