Signaling and G proteins

Dowal, L., Elliott, J., Popov, S., Wilkie, T. M., and Scarlata, S. (2001). Determination of the contact energies between a regulator of G protein signaling and G protein subunits and phospholipase C beta 1. Biochemistry 40, 414-421. 

Whether SI consumption leads to differential effects in EQU producers and nonproducers is less clear in relation to cancer risk. There was no difference in mammographic density following a 1-y SP intervention in PMW compared to a milk protein control and this was unaffected by EQU status (Verheus et al. 2008). However, changes in gene expression, some of which were involved in pathways that are related to cell differentiation, increased cAMP signaling and G-protein-coupled protein metabolism, and increased steroid hormone receptor activity, were more marked in the lymphocytes of EQU producers compared to EQU nonproducers (Niculescu et al. 2007). 

Of the several classes of receptors for endogenous chemical signals [3], two are used as postsynaptic receptors in synaptic transmission ligand-gated ion channels (LGICs) and G protein-coupled receptors (GPCRs Fig. 1). Due to the large number of transmitters and the existence of several receptor types for almost all, postsynaptic receptor activation is the most diversified step of synaptic transmission. Table 1 shows selected neurotransmitter receptors. 

Take one molecule of an incoming signal and make many molecules of an outgoing signal. Kinases, cyclases, and G-proteins amplify the signal. 

Fig. 2. Activation of an intracellular PLC by an extracellular signal (primary messenger) transduced across the membrane via a receptor and G-protein. The products DAG and IP3 that are produced by the PLC catalyzed hydrolysis of phospholipids are secondary messengers...

An, S., Bleu, T. and Zheng, Y., 1999, Transduction of intracellular calcium signals through G protein- mediated activation ofphosphohpase C by recombinant sphingosine 1- phosphate receptors. Mol. Pharmacol. 55 787-794. 

Meyer zu Heiingdoif, D.M., Lass, H., Alemany, R., Laser, K.T., Neumann, R, Zhang, C., Schmidt, M., Rauen, Lf., Jakobs, K.H. and Van Koppen, C.J., 1998, Sphingosine kinase-mediated signaling by G-protein-coupled receptors, EMBO J. 17 2830-2837. 

Gudermann, T., Nurnberg, B., and Schultz, G. Receptors and G proteins as primary components of transmembrane signal transduction. Part 1. G-protein-coupled receptors structure and function./. Mol. Med. 1995, 73, 51-63. 

Initially, phospholipase A2 [1] releases the arachidonate moiety from these phospholipids. TheactivityofphospholipaseA2 is strictly regulated. It is activated by hormones and other signals via G proteins. The arachidonate released is a signaling substance itself However, its metabolites are even more important. 

Figure 14-1. Signaling via G protein-coupled receptors. Ligand binding to its cell-surface receptor initiates interaction of the receptor with the heterotrimeric G protein for which it is specific. A conformational change in the G protein brought about by binding of the ligand-receptor complex promotes exchange of GDP for GTP. The activated Gd-GTP dissociates from the Gp complex and both can interact with effectors, which carry on the signal to the mechanism that implements the cellular response.

Calcium and DAG are second messengers that mediate some responses initiated by signaling from G protein-coupled receptors (Figure 14—3). 

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