Signaling subtype activation

By molecular cloning, five subtypes of G protein-coupled mAChR have been identified and are termed M1-M5 (Caulfield and Birdsall 1998 Wess 1996). Based on their coupling to specific groups of heterotrimeric G proteins, mAChR may be divided into two functional classes M2 and M4 receptors are preferentially coupled to G,/0 signal transduction pathways, whereas Mi, M3, and M5 subtypes activate Gq proteins and downstream effectors (Wess 1996). 

Zhong H, Lee D, Robeva A, Minneman KP. Signaling pathways activated by a,-adrenergic receptor subtypes in PC12 cells. Life Sci 2001 68 2269-2276. 

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. 

The PAR-3 subtype of the PAR family is truncated at the C-terminus limiting its potential to signal intracel-lularly. Furthermore, other than thrombin, there have been no specific activating peptides developed that... 

M2 subtype modulates the amount of REM sleep. If postsynaptic muscarinic receptors of the M2 subtype contribute to REM sleep generation, then pharmacological manipulation of M2-activated signal transduction cascades would be anticipated to alter REM sleep (1.2 on Fig. 5.1). 

Dopamine receptors are found primarily in brain, although they also exist in kidney [33]. Two subtypes of dopamine receptor were initially identified based primarily on differences in their drug specificities and signaling mechanisms. D receptors were found to stimulate adenylyl cyclase activity, while D2 receptors inhibited this enzyme (Fig. 12-6). Subsequently, multiple Dr and D2-like receptors were identified by molecular cloning (Table 12-3) [33], All dopamine receptor subtypes are... 

CREB is also phosphorylated on serine 133 by stimulation of growth factor signaling cascades [63]. This occurs via a complex pathway involving MAPK cascades (Fig. 23-9). Thus, as outlined earlier, nerve growth factor and related neurotrophins that act on receptor tyrosine kinases lead to the successive activation of Ras, Raf, MEK and ERK. Activated ERK then phosphorylates and activates a serine-threonine kinase, RSK, particular subtypes of which directly activate CREB via the phosphorylation of serine 133. 

Fig. 3. Synaptic localization of the mGluRs. The predominant localizations of the seven mGluR subtypes expressed in the CNS. The typical localizations of iGluRs and excitatory amino acid transporters (EAATs) are given, and the regulation of Glu release, iGluR signaling and ion channel activities mediated by the mGluRs is shown.

Davis, K. E., Straff, D. J., Weinstein, E. A., Bannerman, P. G., Correale, D. M., Rothstein, J. D and Robinson, M. B. (1998) Multiple signaling pathways regulate cell surface expression, and activity of the excitatory amino acid carrier 1 subtype of Glu transporter in C6 glioma. J. Neurosci. 18,2475-2485. 

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